Showing posts with label antivirals. Show all posts
Showing posts with label antivirals. Show all posts

Thursday, May 14, 2026

#Ensitrelvir for #Covid19 Postexposure #Prophylaxis in #Household Contacts

 


Abstract

Background

Ensitrelvir, an oral inhibitor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease, is approved in Japan for the treatment of mild-to-moderate coronavirus disease 2019 (Covid-19). Previously, no antiviral agents were approved for postexposure prophylaxis in household contacts of patients with Covid-19.

Methods

In this double-blind, randomized, placebo-controlled trial, we randomly assigned persons who were SARS-CoV-2–negative on local diagnostic testing but were household contacts of a patient with Covid-19 (the index patient) to receive either ensitrelvir (375 mg on day 1 and 125 mg daily on days 2 through 5) or placebo within 72 hours after symptom onset in the index patient. The primary end point was Covid-19 (defined by a central laboratory–confirmed positive reverse-transcriptase–polymerase-chain-reaction assay and the presence of ≥1 of 14 prespecified Covid-19 symptoms lasting ≥48 hours) by day 10 in a household contact in the modified intention-to-treat population (all the participants who underwent randomization, had a central laboratory–confirmed negative RT-PCR test for SARS-CoV-2 at baseline, and received at least one dose of the trial drug or placebo).

Results

The modified intention-to-treat population included 1030 participants in the ensitrelvir group and 1011 in the placebo group. The mean age of the participants was 42.4 years; 71.1% had undergone randomization within 48 hours after symptom onset in the index patient, and 37.0% had at least one risk factor for severe Covid-19. The incidence of Covid-19 was lower in the ensitrelvir group than in the placebo group (2.9% vs. 9.0%; risk ratio, 0.33; 95% confidence interval [CI], 0.22 to 0.49; P<0.001). The incidence of adverse events during the trial was similar in the two groups (15.1% in the ensitrelvir group and 15.5% in the placebo group), as was the incidence of serious adverse events (0.2% in each group). No Covid-19–related hospitalizations or deaths were reported.

Conclusions

Ensitrelvir administered to household contacts of a patient with Covid-19 within 72 hours after symptom onset in the index patient was effective in preventing Covid-19 in the contacts. (Funded by Shionogi; SCORPIO-PEP Japan Registry for Clinical Trials number, jRCT2031230124; ClinicalTrials.gov number, NCT05897541.)

Source: 


Link: https://www.nejm.org/doi/full/10.1056/NEJMoa2509306?query=TOC

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Monday, May 11, 2026

Technical note for disembarkation and onward #management of #passengers and crew in context of an #Andes virus-associated cluster MV Hondius cruise ship - Interim #guidance 8 May 2026 (WHO, edited)

 


Introduction

-- This technical note is intended for public health authorities, port health authorities, and partner agencies involved in the disembarkation, onward travel, monitoring, and follow-up of passengers and crew associated with the MV Hondius event.


Communication

-- Managed by: National health authorities / public health and medical evaluation team / risk communication specialists

-- Effective risk communication is essential to support the safe and orderly disembarkation and onward management of passengers and crew, and to maintain public trust during an evolving public health event

-- Member States should ensure that communication activities are coordinated, timely, and aligned with operational measures described in this technical note. 

-- Passengers and crew should receive clear, consistent and timely information before, during and after disembarkation, including explanations about public health measures, what to expect at each step, and next steps. 

-- Further considerations on risk communication are available in Annex 1.



1. Upon Arrival

Ship regulations

-- Managed by: Ship captain

• The required documentation should be provided to port health authorities, including the valid Ship Sanitation Certificate and the Ship Declaration of Health (or Maritime Declaration of Health).

• The ship should comply with the public health measures recommended by port health authorities, including for measures that need to be applied on board as well as during disembarkation, or medical evacuation.

• The ship captain should notify port health authorities of any person that meets the suspect case definition as assessed by physicians on board.


Communication to passengers and crew members

-- Managed by: captain / evaluation team / crew / communications officer

• Clearly communicate the steps that will be implemented.

• Inform that the disembarkation and onward travel of passengers and crew are being managed through coordinated and controlled public health measures, and that the risk to the general public remains very low.

• Communication should be reassuring yet vigilant, noting that people who have been exposed may still be at risk of developing symptoms and highlighting the importance of recognizing and reporting symptoms early.


2. Upon disembarkation

-- Managed by: national authorities

- Considering the attention attracted by this event, national authorities should ensure arrangements for security and media management in the port receiving the ship.


Management of passengers with symptoms prior to disembarkation

-- Managed by: medical team on board / national health authorities at the port of call

• Duly equipped ambulances should be pre-positioned at the port.

• If a suspected case is identified prior to the arrival of the ship, their medical evacuation to designated health facilities on-shore should be facilitated first, prior to disembarkation of passengers and crew.

• A designated trained team should be able to provide immediate care and ensure the safe and timely transfer to designated health facilities equipped to provide the appropriate level of safe and quality care.

• Any member of the medical team at the port of disembarkation, including ambulance crews, should apply standard and transmission-based precautions when attending cases.

    Perform hand hygiene before putting on personal protective equipment (PPE).

    Put on PPE items including eye protection, respirator (e.g. N95, FPP2), gown, and gloves before assessing, and transferring the case to a designated health facility on shore.

    PPE should be removed once patient transfer has been completed, and hand hygiene performed after removal of PPE items. PPE should be managed as infectious waste.

• Ensure patients use a respiratory (e.g. N95, FPP2) during the transfer.

• Transport of patients should be carefully planned to ensure those sending the patient and receiving them are fully informed and prepared.

• See Annex 2 and 3 for further information.


Steps for disembarkation for passengers and crew members

-- Managed by: national health authorities at the port of call.

• Provide guidance to the crew on organizing the order of disembarkation (e.g. prioritizing passengers according to their location on the ship, followed by crew members, including instructions on how to wear a respirator).

• Staggering the disembarkation of passengers may be considered to ensure safe and efficient disembarkation. Individuals should disembark one by one from the ship.

• Respirators (N95, FPP2) should be provided prior to disembarkation to all passengers and crew members, under the assumption that it cannot be ruled out if contacts are symptomatic until they have been screened.

• All passengers and crew members disembarking should wear a well-fitted respirator{1} prior to disembarkation and until screening is undertaken.

• Individuals should ideally carry minimal hand luggage, with the remaining luggage handled separately by the ship’s company.

• Transport (ideally facilitated through boats or coach) should be available and ready to transport individuals to the onward location. Windows should be kept open for ventilation.


Screening area for passengers and crew members

-- Managed by: national health authorities at the port of call.

• National health authorities will define the best location to organize the screening of disembarking passengers and crew. It may be organized while passengers and crew are exiting the boat one by one or in a designated screening area on shore.

• Screening area(s) should be organized in a dedicated, pre-identified location in the port area, preferably outdoors but allowing for privacy, and with seats (distanced at least one meter apart), access to dedicated bathroom facilities, hand hygiene products and drinking water available in the waiting area.

• If indoors, the room should be well-ventilated (open windows), large enough to maintain distancing of at least one meter between people, have separate entrance and exits with one-way flow to maintain distancing and crowd control, and have provision for personal comfort i.e., toilets, seating (one meter apart), supply of individual water, and waste facilities.

• Toilet and rest facilities should be separate from those for reception and assessment staff.

• Administration and support staff should be allocated to ensure compliance with public health recommendations and are advised to wear medical masks, with access to hand hygiene facilities (soap and water or alcohol-based hand solutions).

• The screening area should ensure that at least one meter distance between the screener and the passenger/crew member is maintained. Temperature checks should be undertaken with non-touch thermometers.

• Respirators, masks and hand hygiene stations should be available in the screening area.

• Adequate environmental cleaning and disinfection of surfaces and shared equipment in the screening area should be performed between screenings.

• Equipped ambulances and their staff should be prepositioned prior to disembarkation, in case a medical evacuation is needed.


Screening and evaluation of passengers and crew members at disembarking

-- Managed by: national health authorities / evaluation team

Note: a team on the ship is currently assessing passengers and crew for exposure and health status. Coordination among this team and the evaluation team at disembarkation is strongly encouraged.

• In coordination with the ship, data on exposures should be examined to facilitate rapid exposure assessments.

• All passengers and crew should be provided with clear information including why measures are in place, what happens next (monitoring, travel, contact points), what symptoms to watch out for, and who to immediately contact 24/7 if any symptom develops.

• Investigation and medical teams should be mindful of the high-stress environment experienced by the passengers and crew and ensure empathy when conducting screening.

• All passengers and crew members are advised to wear a well-fitted respirator (e.g. FFP2, N95) while being assessed by port health authorities.

• During assessment, passengers and crew members will be checked for fever with non-touch thermometers, evaluated for their exposure and any symptoms they might have or have had.

• The above procedures shall be conducted by trained medical teams.

• During evaluation, any passenger or crew member with symptoms compatible with the suspected case definition (see Management of contacts of Andes virus (ANDV) cases from the MV Hondius cruise ship) should be managed as described in the next section.

• Health personnel conducting screening should apply standard IPC precautions, including:

    Perform hand hygiene before and after the screening of contacts.

    Use of gloves if touching travelers and when handling potentially contaminated materials.

    Health personnel are advised to wear a medical mask and eye protection during screening of passengers and crew members at disembarking.

    Medical masks should be disposed of if they become soiled or wet.

    Adequate quantities of PPE items and hand hygiene material should be available in the evaluation area.

• Ideally, those disembarking should be pre-cleared by immigration authorities to avoid the need for contact with immigration staff. If they must pass through immigration, they should do so after screening, and immigration staff should wear a medical mask and have access to hand hygiene facilities (soap and water or alcohol-based hand solutions).


Management of passengers or crew members with symptoms identified at the time of screening

-- Managed by: national health authorities

• During evaluation, if a person presents symptoms compatible with ANDV infection (see case definition in Management of contacts of Andes virus (ANDV) cases from the MV Hondius cruise ship), the medical team should:

    Practice hand hygiene and ensure adequate PPE as described above and in annex 3.

    Isolate the patient in a designated area with a dedicated bathroom and dedicated linen/personal items while transfer for evacuation is organized.

    Initiate the medical evacuation of the person to a designated health facility as indicated above.

    PPE must be changed between patients, and hand hygiene should be performed before putting on PPE, and after removing PPE.

• When transferring, ensure the patient wears a respirator and the health worker wears PPE (eye protection, respirator (e.g. N95, FPP2), gown, gloves).

• Initial symptomatic treatment should be initiated for symptom control and if needed, any supportive care intervention, i.e. oxygen if hypoxemic. A monitoring plan should be put into place to ensure any clinical deterioration is noted in a timely fashion.

• See Annex 2 and 3 for further information.


Mental health and psychosocial support (MHPSS) for passengers and crew members

-- Managed by: MHPSS team, national health authorities.

• Mental health and psychosocial support should be considered for passengers and crew disembarking, as this situation may have generated significant stress in some.

• The availability of psychosocial support could help address anxiety or distress associated with the disembarkation process and perceived health risks.


Management of passenger and crew luggage and belongings

-- Managed by: conveyance operator / competent authorities

• Luggage will be handled after disembarkation by the conveyance operator, in collaboration with competent authorities.

• Passengers and crew members will be able to take their luggage back after screening is completed, in accordance with the protocols established by the competent authorities.


3. After disembarking

Onward travel of asymptomatic passengers and crew members

-- Managed by: national health authorities in country of repatriation

- For further guidance, see Management of contacts of Andes virus (ANDV) cases from the MV Hondius cruise ship.

- Asymptomatic passengers may travel following repatriation from the Canary Islands, provided that

- they have completed the active monitoring and in designated facility or home quarantine. Which includes:

• Public health authorities should conduct daily follow-up for 42 days after disembarkation, during which time the passenger should be advised to avoid contact with other persons through remaining in a designated facilities or at home, depending on national guidelines and capacities. 

• Follow-up may occur by telephone, messaging, telehealth, or in person.

• Passengers who are healthcare workers should refrain from returning to work for designated period.

• Passengers should avoid contact with other household members, and where possible and remain in a separate room.

• In case social interactions are unavoidable, passenger should wear a FFP2 or N95 respirator, practice physical distancing, and observe regular hand hygiene.

• All travel, nationally and internationally, should be discouraged for 42 days.

• Movement of the passenger out of the jurisdiction of public health authorities in charge of their follow-up may be allowed for life-threatening or humanitarian reasons, provided that arrangements are made with the public health authorities in the jurisdiction at destination, including internationally through IHR channels.

• During daily follow-up, any symptoms: temperature, fever, fatigue or malaise, muscle ache, headache, gastrointestinal symptoms, respiratory symptoms, should be promptly reported using a contact follow-up form.

• Any passengers developing symptoms compatible with hantavirus infection should be promptly isolated, clinically evaluated and tested.

• Passengers should receive:

    Written information on symptoms to look out for.

    Emergency contact numbers.

    Instructions regarding healthcare seeking and testing.


Crew management

-- Managed by: cruise operator / competent authorities

• Medical care, including public health preventive measures, for crew members should be provided in accordance with the Maritime Labour Convention, 2006, as amended (MLC, 2006)

• Crew members should not resume duty on another ship until they complete the active monitoring and in designated facility or home quarantine (as above)


Management of deceased persons confirmed for ANDV infection on the ship

-- Managed: national authorities at port of call.

- Transmission of ANDV from deceased persons has not been documented, and viral load decreases before terminal illness; however, other respiratory pathogens (e.g., tuberculosis) have been transmitted from human remains. Thus, as exposure to bodily fluids and respiratory secretions may occur during handling of remains, standard IPC precautions should be applied when managing deceased suspected, probable, or confirmed cases.

• Personnel handling remains should apply standard IPC precautions and wear appropriate PPE, including gloves, gown, medical mask, and eye protection where exposure to bodily fluids or respiratory secretions is possible.

• Hand hygiene should be performed before and after PPE use and after contact with the body or contaminated materials.

• Unnecessary manipulation of the body and aerosol-generating procedures should be avoided.

• The body should be placed in a leak-proof body bag if needed and handled according to national procedures.

• Environmental cleaning and disinfection of potentially contaminated surfaces and equipment should be performed using appropriate disinfectants.

• International repatriation of remains may proceed according to national and international regulations.


Ship disinfection

-- Managed by conveyance operator and competent authorities

• The ship should be inspected for rodents, cleaned, disinfected and appropriate rodent control measures implemented, as appropriate, in accordance with the Integrated Management Plan of the Ship and WHO guidance, and as per advice of the competent authority.

• The ship shall cease to be regarded as affected when the competent authority is satisfied with the measures implemented, and there are no conditions on board that could constitute a public health risk.

• Staff involved in sanitary procedures on board the ship should wear adequate PPE (including eye protection, respirator, gown, and gloves).


Plans for updating

-- WHO continues to monitor the situation closely for any changes that may affect this interim guidance. 

-- Should any factors change, WHO will issue a further update. 

-- Otherwise, this interim guidance will expire one year after the date of publication.


References

1. World Health Organization. International Health Regulations (2005) – As amended in 2014, 2022 and 2024. https://apps.who.int/gb/bd/pdf_files/IHR_2014-2022-2024-en.pdf

2. World Health Organization. WHO Guideline on Contact Tracing; 2025. https://www.who.int/publications/i/item/9789240102965

3. World Health Organization. Handbook for Management of Public Health Events on Board Ships; 2016. https://www.who.int/publications/i/item/handbook-for-management-of-public-health-events-on-board-ships

4. World Health Organization. Vector Surveillance and Control at Ports, Airports, and Ground Crossings; 2016. https://www.who.int/publications/i/item/vector-surveillance-and-control-at-ports-airports-and-ground-crossings

5. World Health Organization. Guide to Ship Sanitation. 3rd edition; 2011. https://www.who.int/publications/i/item/9789241546690

6. World Health Organization. Handbook for inspection of ships and issuance of ship sanitation certificates; 2011. https://www.who.int/publications/i/item/handbook-for-inspection-of-ships-and-issuance-of-ship-sanitation-certificates

7. World Health Organization. Considerations for strengthening international information sharing for tracing and managing infectious disease cases and contact persons: Interim Guidance; 2026. https://www.who.int/southeastasia/internal-publications-detail/sewhe09022601

8. World Health Organization. World Health Organization. A decision framework for effective, equitable and context-specific public health and social measures during public health emergencies: decision navigator.

9. EU Healthy Sailing. Evidence-based guidelines for the specificities and needs of medical operations in expedition passenger ships. 2026

10. WHO and ICRC. Basic Emergency Care. Approach to the acutely ill and injured. 2018. https://www.who.int/publications/i/item/basic-emergency-care-approach-to-the-acutely-ill-and-injured


Annex 1. Risk communication

-- Effective risk communication is essential to support the safe, orderly, and dignified disembarkation and onward management of passengers and crew members, and to maintain public trust during an evolving public health event. 

-- Member States should ensure that communication activities are coordinated, timely, and aligned with operational measures described in this technical note.

• Ensure that passengers and crew receive clear, consistent and timely information before, during and after disembarkation, including explanations of public health measures, what to expect and next steps.

• Ensure communication materials are available in the relevant languages of passengers and crew and in accessible formats.

• Communicate clearly that the disembarkation and onward return of passengers and crew are being conducted through coordinated and controlled public health procedures, and that the risk to the wider public remains low.

• Communication should be reassuring yet vigilant, noting that people who have been exposed may still be at risk of developing symptoms and highlighting the importance of recognizing and reporting symptoms early.

• Acknowledge openly what is known and what remains uncertain, that investigations are ongoing and that recommendations may be updated as new epidemiological or laboratory evidence becomes available.

• Explain that changes in guidance reflect standard precautionary public health practice.

• Provide passengers and crew with written and verbal information on symptoms to monitor, duration, procedures if symptoms develop and contact details for public health authorities responsible for follow-up.

• Promote early reporting of symptoms and cooperation with monitoring arrangements and any other public health measure advised while traveling home.

• Ensure communication materials and briefings emphasize respect for the dignity, privacy and rights of passengers and crew and explicitly discourage stigma, discrimination, or blame.

• Ensure that communication at points of entry (ports, airports, transit hubs) is coordinated across agencies and consistent in messaging to avoid confusion or contradictory messages.

• Provide host communities, transit authorities, and destination countries with clear public information on the rationale for measures in place, what to expect, and what actions are not required.

• Establish clear channels for two-way communication, allowing passengers and crew to ask questions, raise concerns, and seek clarification throughout disembarkation and onward management.

• Monitor public perceptions, media coverage, and misinformation related to the event and adapt communication content and tone as needed, in coordination with WHO and relevant partners.


Annex 2. IPC for healthcare workers caring for suspected or confirmed cases

• Suspected, probable or confirmed cases must be isolated in single rooms (one room per case).

• In addition to standard precautions, implement transmission-based precautions when providing care to suspected or confirmed cases.

• Those providing care should wear personal protective equipment prior to entering the isolation room.

    Perform hand hygiene before donning PPE.

    PPE items include: eye protection, respirator (e.g. N95, FPP2), gown, gloves when providing direct patient care.

    PPE should be removed and appropriately disposed of when exiting the isolation room, and hand hygiene must be performed after removal of PPE items.

• Ensure adequate indoor ventilation.

• Routine environmental cleaning and disinfection should be performed using regular disinfectants.

• Medical waste and used linen should be handled as per existing procedures.

• When transferring, ensure the patient wears a respirator and the healthcare worker wears PPE (eye protection, respirator (e.g. N95, FPP2), gown, gloves).

• Transport of patients should be carefully planned to ensure sending/receiving ends are fully informed and prepared.


Annex 3. Considerations on clinical management of suspected and confirmed patients

-- Medical management of a person with suspected, probable or confirmed hantavirus infection should be structured through standard protocols using appropriate PPE (see above), including:

• Severity-based triage of the condition using clinical and physiological measures (see WHO Basic Emergency Care).

• Systematic assessment, and rapid emergency action to address problems in Airway, Breathing, Circulation, Disability [ABCDE].

• Establishing a diagnosis is a priority (PCR and serology testing), but all patients should be managed according to the severity of disease. Outbreak case definitions are not a substitute for clinical judgment.

• High-quality and anticipatory supportive care should be provided.

    Oxygen and availability of respiratory support should be prioritised.

    * Deterioration after the prodromal phase can be precipitous (over hours). Anticipatory actions should include careful monitoring and ensuring proximity to intensive care facilities for cardiovascular support, mechanical ventilation, and ideally extracorporeal membrane oxygenation.

    * Shock should be treated according to existing clinical guidelines for sepsis.

    * Ensure monitoring of vital signs and renal function (through clinical and biochemical assays). Investigation and monitoring of platelet count and proteinuria should be in place as these provide early insight into adverse prognosis, and imminent acute kidney injury respectively.

    * There are no proven antiviral treatments for hantavirus. Off-label use of favipiravir, remdesivir and other existing drugs have been used. Such use must be accompanied by detailed clinical data capture under monitored use. Mechanistically, remdesivir is less favourable compared with favipiravir due to its relatively reduced action against segmented viruses such as hantavirus).

• Direct evidence related to the use of corticosteroids in hantavirus infection for pulmonary or renal syndromes is limited. A single randomized controlled trial of patients with Andes virus hantaviral infection with cardiopulmonary syndrome in Chile did not demonstrate a benefit from high dose corticosteroid treatment but was underpowered to detect a moderate difference between arms.

• Routine antibiotic administration is not indicated for known hantavirus disease. However, for those presenting with symptoms of acute respiratory infection, bacterial infection must be considered. Suspicion of superadded bacterial infection is also an indication for antibiotic treatment based on clinical assessment.


Annex 4. Considerations on laboratory diagnosis

NOTE. Further information on laboratory diagnosis will be provided in a separate document and will cover additional aspects.

• Laboratory diagnosis of hantavirus infection relies on either molecular detection of viral RNA and serological detection of antibodies, with the choice depending on the interval between symptom onset and sample collection.

• By the time symptoms develop, viremia is often already at or near its peak, and both IgM and IgG antibodies may be detectable. IgM levels begin to decline over the following weeks and typically disappear within about three months, whereas IgG appears slightly later and may remain elevated for many years.

• For molecular detection, whole blood is recommended, while serum and blood clot can also be used. Serum is the preferred specimen for serology, although plasma from whole blood is also acceptable. Samples should be collected in sterile plastic tubes with screw caps.


Testing of suspected cases

• Suspected cases should be tested using an Andes virus–specific RT-PCR protocol, as outlined in reference laboratory procedures posted on the WHO EIS Platform and in the WHO Disease Outbreak News. In the absence of Andes virus-specific RT-PCR, a pan-hantavirus PCR can be used, and sequencing should be performed to confirm Andes virus.

• Molecular detection by RT-PCR, whether conventional or real-time, can confirm infection at any point during the acute phase, up to approximately ten days after symptom onset.

• If a sample has been collected more than 10 days after onset, a negative RT-PCR result in a properly collected and preserved sample, only rules out infection when serological testing is also negative, provided that enough time since last exposure has elapsed to allow development of anti-Andes virus specific antibodies.

• Positive cases without an epidemiological link to a confirmed or probable case should be systematically sequenced.


Testing of asymptomatic contacts for research purposes

• Routine testing of asymptomatic contacts is not mandatory for public health purposes.

• Regular (e.g. weekly) RT-PCR testing of asymptomatic contacts, on specimens such as blood, saliva, oral swabs and nasopharyngeal swabs, could be considered for research purposes to better understand virus shedding and transmission dynamics.

• However, testing should NOT be used to determine the end of the follow-up period, which remains fixed at 42 days after last exposure regardless of test results.

• When testing capacity is limited, symptomatic contacts must always be prioritised for diagnostic testing because they are more likely to be infected and require timely clinical evaluation.

• Serological testing at the beginning and end of the follow-up period may also be considered to ascertain serological status of contacts.

© World Health Organization 2026. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO license.

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{1} The recommendation for contacts to wear a well-fitted respirator (N95, FFP2) until screening is undertaken is a precautionary source control measure aimed at reducing the risk of onward transmission from individuals who might be symptomatic and pre-symptomatic.

Source: 


Link: https://www.who.int/publications/m/item/who-technical-note-for-the-disembarkation-and-onward-management-of-passengers-and-crew-in-the-context-of-an-andes-virus-associated-cluster-mv-hondius-cruise-ship

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Wednesday, May 6, 2026

Computational #design of an ultrapotent #deltacoronavirus miniprotein #inhibitor

 


Significance

Multiple porcine deltacoronavirus (PDCoV) spillovers occurred in Haiti and there are currently no vaccines or therapeutics approved for use in humans. We computationally designed PDCoV miniprotein inhibitors and identified one (MB11) that potently and broadly neutralizes distantly related delta-coronaviruses. MB11 is resistant to multiple biochemical stresses, an ideal property for easy storage and delivery. These data pave the way for developing therapeutics to prepare for possible future PDCoV outbreaks.


Abstract

Multiple spillovers of porcine deltacoronavirus (PDCoV) into humans in Haiti highlight its zoonotic potential and the need for targeted interventions. No approved vaccines or therapeutics are available for use in humans against any DCoVs. Here, we report the de novo design of PDCoV miniprotein inhibitors (aka minibinders, MBs) and show that one of them, MB11, binds with picomolar affinity to the PDCoV receptor-binding domain (RBD). MB11 potently inhibits PDCoV, outcompeting monoclonal antibodies, and cross-reacts with and broadly neutralizes a panel of distantly related DCoVs. We determined a cryoelectron microscopy structure of MB11 bound to the PDCoV RBD which reveals the molecular basis of broad DCoV neutralization through interference with host receptor engagement. Deep mutational scanning of the PDCoV RBD reveals that MB11 has a high barrier to viral escape with only few mutations mediating escape without dampening APN receptor binding. MB11 resists stringent biochemical stresses, including high temperature, low pH, and proteolysis, which may enable delivery to various tissues for viral inhibition. This work delineates a prime candidate for clinical evaluation against PDCoV infection and for pandemic preparedness.

Source: 


Link: https://www.pnas.org/doi/abs/10.1073/pnas.2533456123?af=R

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Monday, May 4, 2026

#Niclosamide Inhibits the #Replication of Highly Pathogenic Avian #Influenza #H5Nx Viruses and Antiviral-Resistant #Mutants

 


Highlights

• Niclosamide blocks the replication of highly pathogenic avian influenza H5 viruses

• Niclosamide is effective against H5 viruses with antiviral-resistant substitutions

• Niclosamide has potential as host-targeting anti-influenza drug


Abstract

The recurrent spillover of highly pathogenic avian influenza (HPAI) H5 viruses into humans represents a major public health concern that is exacerbated by the emergence of drug-resistant viral variants. Host-targeting antiviral approaches, including drug repurposing, offer a promising alternative to conventional virus-directed therapeutics. Here, we evaluated the antiviral activity of niclosamide, an FDA-approved anthelmintic drug, against four HPAI A(H5Nx) viruses, two A(H5N1), one A(H5N6), and one A(H5N8), recently isolated from human cases. Niclosamide inhibited all four viruses in plaque reduction assays with MDCK cells, with low inhibitory concentration 50% (IC50) values (0.68–1.40 μM) and minimal cytotoxicity at effective concentrations. These values were more potent than the IC50 values observed for the RdRp inhibitor favipiravir. Niclosamide treatment plus either baloxavir marboxil or favipiravir resulted in additive or near-additive interactions, as indicated by synergy scores of ±10. Importantly, niclosamide retained antiviral activity against HPAI A(H5Nx) viruses bearing resistance-associated amino acid substitutions (i.e., PA-I38T, baloxavir resistance and PB1-K229R, favipiravir resistance), consistent with its host-directed mechanism of action. Although there are barriers to be overcome such as a narrow therapeutic window, largely attributable to its poor bioavailability and some cytotoxicity, our findings suggest niclosamide has potential as a host-targeting therapeutic option against emerging zoonotic influenza viruses, particularly in settings involving antiviral-resistant escape mutants.

Source: 


Link: https://www.sciencedirect.com/science/article/pii/S016635422600080X?via%3Dihub

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Thursday, April 30, 2026

Characterizing #viral #clearance kinetics in acute #influenza

 


Abstract

Pharmacometric assessment of antiviral efficacy in acute influenza informs treatment decisions and pandemic preparedness. We characterized natural viral clearance in acute influenza to guide phase II trial design using simulations based upon observed data. Standardized duplicate oropharyngeal swabs were collected daily over 14 days from 80 untreated low-risk Thai adults, with viral densities measured using quantitative polymerase chain reaction. We evaluated three models to describe viral clearance: exponential, bi-exponential and growth-and-decay. The growth-and-decay model provided the best fit, but the exponential decay model was the most parsimonious. The median viral clearance half-life was 10.3 h (interquartile range (IQR): 6.8–15.4h), varying by influenza type: 9.6 h (IQR: 6.2–13.0 h) for influenza A and 14.0 h (IQR: 10.3–19.3 h) for influenza B. Simulated trials using parameters from the exponential decay model showed that 148 patients per arm provide over 90% power to detect treatments accelerating viral clearance by 40%. Variation in clearance rates strongly impacted the power; doubling this variation would require 232 patients per arm for an antiviral with a 60% effect size. A sampling strategy with four swabs per day reduces the required sample size to 81 per arm while maintaining over 80% power. We recommend this approach to assess and compare current anti-influenza drugs.


This article is part of the Theo Murphy meeting issue ‘Evaluating anti-infective drugs’.

Source: 


Link: https://royalsocietypublishing.org/rstb/article/381/1949/20240351/481559/Characterizing-viral-clearance-kinetics-in-acute

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#Antiviral treatment for #influenza

 


Abstract

Seasonal influenza is a widespread acute respiratory infection that causes significant illness and death worldwide. Two major antiviral classes are neuraminidase inhibitors (NAIs) and polymerase inhibitors. NAIs, including oseltamivir, zanamivir, peramivir and laninamivir, block viral release, while polymerase inhibitors such as baloxavir disrupt viral RNA replication. Early administration within 48 h of symptom onset reduces illness duration, severity and complications, particularly in high-risk groups. Oseltamivir is the most widely studied NAI, demonstrating reduced viral shedding, faster symptom resolution and lower complication rates, though gastrointestinal side effects are common. Higher doses generally do not improve outcomes compared to standard dosing. Zanamivir is more effective against influenza B and is inhibitory for most influenza A viruses resistant to oseltamivir, but the inhaled formulation is less suitable for patients with severe illness or airway disease. Intravenous (IV) zanamivir is approved for hospitalized influenza patients in some countries. Peramivir offers IV treatment options, while laninamivir is mainly used in Japan. Baloxavir shows superior viral load reduction and comparable symptom relief to oseltamivir in outpatients, though resistance variants can emerge. Favipiravir and newer polymerase inhibitors are under investigation. Combination therapies may enhance recovery, with limited evidence. Overall, timely antiviral use is critical to reducing influenza’s burden.


This article is part of the Theo Murphy meeting issue ‘Evaluating anti-infective drugs’.

Source: 


Link: https://royalsocietypublishing.org/rstb/article/381/1949/20240344/481548/Antiviral-treatment-for-influenza

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Thursday, April 23, 2026

Oral #Nirmatrelvir – Ritonavir for #Covid19 in Higher-Risk #Outpatients

 


Abstract

Background

Nirmatrelvir–ritonavir has been shown to reduce progression to severe illness from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in unvaccinated high-risk outpatients. The effectiveness of nirmatrelvir–ritonavir in persons who have been vaccinated, infected naturally, or both is unclear.

Methods

In two open-label platform trials (PANORAMIC in the United Kingdom and CanTreatCOVID in Canada), we enrolled higher-risk adults (≥50 years of age or ≥18 years of age with coexisting conditions) in the community who tested positive for SARS-CoV-2 and had been unwell for 5 days or less. The participants were randomly assigned to receive usual care plus nirmatrelvir (300 mg)–ritonavir (100 mg) twice a day for 5 days or to receive usual care alone. The primary outcome was hospitalization or death from any cause within 28 days after randomization.

Results

From December 8, 2021, to September 30, 2024, a total of 3516 participants in the PANORAMIC trial and 716 participants in the CanTreatCOVID trial underwent randomization. In the PANORAMIC trial, 14 of 1698 participants (0.8%) in the nirmatrelvir–ritonavir group and 11 of 1673 participants (0.7%) in the usual-care group were hospitalized or died (adjusted odds ratio, 1.18; 95% Bayesian credible interval, 0.55 to 2.62; probability of superiority, 0.334). In the CanTreatCOVID trial, 2 of 343 participants (0.6%) in the nirmatrelvir–ritonavir group and 4 of 324 participants (1.2%) in the usual-care group were hospitalized or died (adjusted odds ratio, 0.48; 95% Bayesian credible interval, 0.08 to 2.23; probability of superiority, 0.830). In a substudy involving 634 participants, viral load was reduced by the end of treatment with nirmatrelvir–ritonavir. Serious adverse events with nirmatrelvir–ritonavir were reported in 9 participants in the PANORAMIC trial and in 4 participants in the CanTreatCOVID trial.

Conclusions

In two open-label trials, nirmatrelvir–ritonavir did not reduce the incidence of hospitalization or death among vaccinated higher-risk participants with SARS-CoV-2 infection. (Funded by the National Institute for Health and Care Research, and others; PANORAMIC ISRCTN number, 2021-005748-31; CanTreatCOVID ClinicalTrials.gov number, NCT05614349.)

Source: 


Link: https://www.nejm.org/doi/full/10.1056/NEJMoa2502457?query=TOC

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Wednesday, April 22, 2026

#Ensitrelvir for the #treatment of hospitalized adults with #COVID19: an international phase 3 randomized placebo-controlled trial

 


Abstract

Background

Antivirals remain an important treatment strategy for persons who experience severe and life-threatening COVID-19. Ensitrelvir is an oral 3CL protease inhibitor with potent antiviral activity.

Methods

We conducted an international randomized, placebo-controlled trial of ensitrelvir with standard of care (SOC) among adults hospitalized for COVID-19. The primary outcome was clinical recovery assessed by the Days to Recovery Scale through Day 60 (DRS-60), analyzed using a Van Elteren test.

Results

From 2023 to 2025, 589 participants received blinded study treatment (293 ensitrelvir and 296 placebo). Median age was 69 years, 49% were female, 68% were White, and SOC commonly included corticosteroids (61% and 54%) and remdesivir (62% and 60%) in ensitrelvir and placebo groups, respectively. Median DRS-60 category was 6 (IQR: 3-15) in the ensitrelvir and 5.5 (IQR: 3-12) in the placebo group (p=0.19), and the OR was 0.82 (95% CI: 0.62-1.09) for a better DRS-60 category with ensitrelvir. Ensitrelvir participants had lower detectable viral antigen in plasma at Day 5 (13.4% vs 25.1%; p<0.001). There was no difference in secondary clinical outcomes or pre-specified safety outcomes, though the mortality rate was 6.1% vs 4.4% and the frequency of hemorrhagic events was 3.4% vs 0.3% among ensitrelvir and placebo groups, respectively.

Conclusions

Ensitrelvir treatment did not improve clinical recovery in addition to SOC for adults hospitalized for COVID-19. The lower illness severity in the Omicron era compared to earlier periods in the COVID-19 pandemic, and high use of remdesivir and corticosteroids, may have contributed to the lack of clinical benefit.

Source: 


Link: https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciag272/8660678?redirectedFrom=fulltext

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Tuesday, April 21, 2026

Timing of #Remdesivir Initiation and Clinical #Outcomes in Hospitalized Patients with #COVID19 Who Are at High Risk of Disease Progression in #Japan: A Health Insurance Claims Database Study

 


Abstract

Early initiation of remdesivir (RDV) is recommended to improve COVID-19 outcomes, but real-world studies describing patterns of RDV use and related outcomes among Japanese COVID-19 patients at high-risk of severe outcomes or death are limited. This claims-based cohort study included 60,165 high-risk patients hospitalized with COVID-19 between October 2021 and June 2023 using the DeSC Healthcare claims database. Patients were categorized into early-RDV (within 2 days of hospital admission), late-RDV (between day 3 and day 7), and no-RDV groups based on RDV initiation timing. Descriptive analyses were performed according to RDV groups. Of the study patients, ≥85% were very elderly (≥75 years). Approximately 39% of patients received early RDV, 2% received late RDV, and 59% received no RDV. By day 28, the proportion of alive discharge for early-, late-, and no-RDV groups was 74.9%, 63.1%, and 71.8%, respectively. The mortality for early-, late-, and no-RDV groups was 7.7%, 8.8%, and 8.4%, respectively. Future hypothesis-driven studies with an appropriate adjustment for confounders are needed to formally evaluate the impact of RDV initiation timing on clinical outcomes in this high-risk, predominantly late-elderly population in Japan.

Source: 


Link: https://www.mdpi.com/1999-4915/18/4/479

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Thursday, April 16, 2026

The virus entry #inhibitor ARN-75039 provides therapeutic #protection against #Lassa virus infection in guinea pigs

 


Abstract

Lassa virus (LASV), a member of the Arenaviridae family, causes Lassa fever. There are no vaccines available for prevention of Lassa fever, and the primary therapeutic for treatment (ribavirin) has questionable antiviral activity and no formal approval for use. Here, we evaluated ARN-75039, an orally bioavailable broad-spectrum mammarenavirus entry inhibitor, against LASV infection in outbred Hartley guinea pigs exposed to a guinea pig–adapted LASV. ARN-75039 was administered for 14 days either 3 or 7 days postexposure (dpe) to LASV. In the first two studies, once-daily dosing at 3 dpe provided protection against lethal infection. A third study with twice-daily dosing at 7 dpe also achieved protection. Both drug regimens offered 100% protection at the lowest tested doses of 3.75 mg/kg (once-daily administration) or 7.5 mg/kg (twice-daily administration). ARN-75039–treated animals exhibited minimal disease signs and undetectable viremia. These results suggest that ARN-75039, for which a phase 1 human clinical trial has now been completed, may offer robust protection against LASV infection.

Source: 


Link: https://www.science.org/doi/10.1126/scitranslmed.adx0938

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Wednesday, April 8, 2026

#Genetic and #biological characterization of a #duck-origin clade 2.3.4.4b #H5N6 avian #influenza virus reveals partial #mammalian #adaptation

 


Highlights

• Duck-origin H5N6 virus A/Duck/Jiangsu/628/2022 shares high homology with the human strain A/Yangzhou/125/2022.

• The 628 strain shows mammalian adaptation markers: HA mutations enhance human receptors affinity and NA mutations reduce sensitivity to neuraminidase inhibitors.

• Limited airborne transmission but detectable droplet-mediated spread suggests increased mammalian transmission risk.


Abstract

Clade 2.3.4.4b H5Nx highly pathogenic avian influenza viruses (HPAIVs) have caused extensive outbreaks in poultry worldwide. H5 HPAIVs have caused sporadic but severe human infections in China, representing a persistent zoonotic threat. Here, we identified a duck-origin H5N6 HPAIV (A/Duck/Jiangsu/628/2022) through routine surveillance and assessed its biological characteristics and mammalian pathogenesis. Phylogenetic analysis revealed > 98% nucleotide identity between strain 628 and the concurrent human H5N6 strain A/Yangzhou/125/2022. Molecular characterization identified multiple mammalian adaptation markers: hemagglutinin substitutions (S137A, T160A, T192I) associated with enhanced human receptor binding; neuraminidase mutations (I117T, D198N) linked to reduced neuraminidase inhibitor susceptibility; and polymerase complex changes (PB1-D622G, PA-K142Q) conferring increased mammalian cell replication. In vitro studies demonstrated that 628 virus replicated more efficiently in mammalian than in avian cells and exhibited dual receptor-binding specificity. Mouse pathogenicity assays revealed moderate virulence with progressive lung pathology. Critically, transmission experiments confirmed both direct contact and airborne transmission capabilities of 628 in guinea pigs. These findings demonstrate that circulating H5N6 viruses have acquired partial mammalian adaptation while retaining avian fitness, significantly elevating pandemic potential. Enhanced surveillance of wild bird populations, poultry farms, and live poultry markets is urgently needed to develop effective prevention and control strategies.

Source: 


Link: https://www.sciencedirect.com/science/article/abs/pii/S037811352600146X?via%3Dihub

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Sunday, April 5, 2026

Next-generation #inhibitors of #SARS-CoV-2 #Mpro overcome the deficiencies of #Paxlovid

 


Abstract

It remains elusive to design peptidomimetic inhibitors of SARS-CoV-2 main protease (Mpro) refractory to multiple deficiencies of Paxlovid (ritonavir-boosted nirmatrelvir), pertaining mainly to E166X mutations-conferred drug resistance and inherent pharmacokinetic limitations to nirmatrelvir. We identify via virtual screening an iso-quinoline P1 moiety in place of the traditional γ-lactam and design iso-quinoline-containing inhibitors with high affinity for Mpro and its nirmatrelvir-resistant E166X mutants. Further optimization at P4 cultivates distinctive peptidomimetic inhibitors with drastically improved pharmacokinetic properties and significantly enhanced antiviral efficacy independent of ritonavir. Two such inhibitors, FD3-32 and FD3-36, also potent against SARS-CoV-1 and MERS-CoV Mpro, are more effective as a monotherapy regimen than Paxlovid in reducing viral loads in vivo and protecting infected male mice from acute lung injury. Here, we report the discovery of next-generation SARS-CoV-2 Mpro inhibitors that overcome the deficiencies of Paxlovid, promising efficacious antivirals critical for mitigating the current and future pandemics of coronaviruses.

Source: 


Link: https://www.nature.com/articles/s41467-026-71436-6

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Tuesday, March 31, 2026

Antiviral activities of multiple #antivirals against highly pathogenic avian #influenza A #H5N1 in vitro and in mice

 


ABSTRACT

In 2024, a bovine H5N1 strain was first isolated from dairy cows in Texas and confirmed to transmit cross-species to humans. Therefore, research on treatments for human infection should be accelerated. In our study, the antiviral effects of baloxavir acid (BXA), oseltamivir carboxylate (OSC), EIDD-1931 (NHC), and ribavirin (RBV) against five H5N1 strains were evaluated in vitro. Cell viability and viral replication were measured to assess the antiviral effects. The results showed that the EC50 of BXA treatment was the lowest. The BXA/NHC and BXA/OSC combination treatments showed more potent inhibitory effects than each monotherapy. The 15 mg/kg baloxavir marboxil (BXM) / 125 mg/kg molnupiravir (MNP) and the 15 mg/kg BXM / 10 mg/kg oseltamivir phosphate (OSP) were tested in BALB/c mice. The mice were inoculated with 10 times the 50% mouse lethal dose (10 MLD50) of bovine H5N1 virus. Treatments began 1-day post-infection (1 dpi) and were administered orally twice daily for 5 or 7 days. Changes in body weight, clinical signs, and survival were monitored; lung and brain tissues were collected for virological, immunological, and histological analyses. Most mice died from severe neurological symptoms. Compared with the 5-day treatment, the 7-day treatment effectively inhibited viral replication and increased survival rates to 50% in BXM, BXM/MNP, and BXM/OSP treatments. Mice treated with BXM/MNP or BXM/OSP combination therapy showed lower viral yields in the lungs than those treated with BXM alone. The results provide a reference for human treatment, and extending the 7-day combination treatment should be considered.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/journals/temi20

Link: https://www.tandfonline.com/doi/full/10.1080/22221751.2026.2645843

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Monday, March 30, 2026

Prompt and Intensive #Antiviral #Chemoprophylaxis in Nursing Home #Influenza #Outbreaks

 


Key Points

-- QuestionIs initiation of antiviral chemoprophylaxis with oseltamivir for 70% or more of eligible nursing home (NH) residents within 2 days of outbreak detection associated with lower 14-day and 30-day mortality and hospitalization compared with a nonintensive approach?

-- FindingsIn this cohort study of 404 influenza outbreaks across 318 NHs with 35 086 resident-trial observations using a sequential target trial emulation and the randomize-censor-weight approach, hospitalization but not death was lower at 14 days post outbreak in NHs that implemented intensive antiviral chemoprophylaxis; 30-day estimates were directionally similar but less precise.

-- MeaningResults of this study suggest that clinicians should promptly initiate antiviral chemoprophylaxis in at least 70% of NH residents within 2 days of an influenza outbreak to markedly reduce influenza-related hospitalizations.


Abstract

Importance  

Influenza outbreaks in nursing homes (NHs) can cause high morbidity and mortality. Antiviral chemoprophylaxis with oseltamivir is recommended, yet optimal implementation strategies remain unclear.

Objective  

To examine whether initiating antiviral chemoprophylaxis for 70% or more of eligible NH residents within 2 days of influenza outbreak detection is associated with lower all-cause mortality and hospitalization at 14 and 30 days.

Design, Setting, and Participants  

Retrospective cohort study using a sequential cluster-randomized target trial emulation and randomize-censor-weight approach for influenza outbreaks (September 1, 2018–May 31, 2022) in 12 US NH corporations. Eligibility criteria were age 18 years or older, present on the outbreak-detection day, no antiviral use in the preceding 7 days, no influenza in the past 14 days, and complete baseline data. Residents were followed up until hospitalization or death, an NH discharge to a nonacute-care location, or the end of follow-up. Data were analyzed from February 2023 to January 2026.

Exposures  

Intensive antiviral chemoprophylaxis with oseltamivir (≥70% of eligible residents within 2 days of outbreak detection) or nonintensive antiviral chemoprophylaxis (0% to <70% of eligible residents).

Main Outcomes and Measures  

Outcomes were all-cause death and hospitalizations within 14 and 30 days of outbreak detection. Discrete-time hazard models with pooled logistic regression were applied to estimate weighted risks, risk differences (RDs), and risk ratios (RRs).

Results  

Among 404 outbreaks in 318 NHs, 35 086 resident-trial observations (29 683 residents; median age 78 [IQR, 68- 86] years; 60% women; 81% White; 76% vaccinated) met eligibility criteria. Intensive oseltamivir prophylaxis was randomized to 17 155 observations; 17 931 were randomized to nonintensive care. At 14 days, intensive prophylaxis vs nonintensive yielded an RD of –0.06% (95% CI, −0.73% to 0.93%) and an RR of 0.96 (95% CI, 0.56-1.57) for death, and an RD of –0.96% (95% CI, −1.78% to −0.19%) and an RR of 0.79 (95% CI, 0.64-0.96) for hospitalization. At 30 days, the hospitalization differences persisted but were less precise and there continued to be no difference in death.

Conclusions and Relevance  

Study results suggest that clinicians should initiate antiviral chemoprophylaxis for at least 70% of eligible NH residents within 2 days of outbreak detection to lower risk of hospitalization.

Source: 


Link: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2846967

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