#SARS-CoV-2 infection #enhancement by #amphotericin B: implications for disease management

ABSTRACT

Severe coronavirus disease 2019 (COVID-19) patients who require hospitalization are at high risk of invasive pulmonary mucormycosis. Amphotericin B (AmB), which is the first-line therapy for invasive pulmonary mucormycosis, has been shown to promote or inhibit replication of a spectrum of viruses. In this study, we first predicted that AmB and nystatin had strong interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins using in silico screening, indicative of drugs with potential therapeutic activity against this virus. Subsequently, we investigated the impact of AmB, nystatin, natamycin, fluconazole, and caspofungin on SARS-CoV-2 infection and replication in vitro. Results showed that AmB and nystatin actually increased SARS-CoV-2 replication in Vero E6, Calu-3, and Huh7 cells. At optimal concentrations, AmB and nystatin increase SARS-CoV-2 replication by up to 100- and 10-fold in Vero E6 and Calu-3 cells, respectively. The other antifungals tested had no impact on SARS-CoV-2 infection in vitro. Drug kinetic studies indicate that AmB enhances SARS-CoV-2 infection by promoting viral entry into cells. Additionally, knockdown of genes encoding for interferon-induced transmembrane (IFITM) proteins 1, 2, and 3 suggests AmB enhances SARS-CoV-2 cell entry by overcoming the antiviral effect of the IFITM3 protein. This study further elucidates the role of IFITM3 in viral entry and highlights the potential dangers of treating COVID-19 patients, with invasive pulmonary mucormycosis, using AmB.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00519-25?af=R

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The first reported case of #candidemia caused by the novel #Candida tropicalis diploid sequence type 1515

Abstract

Introduction: 

Since the dawn of the new millennium, Candida species have been increasingly implicated as a cause of both healthcare-associated as well as opportunistic yeast infections, due to the widespread use of indwelling medical devices, total parenteral nutrition, systemic corticosteroids, cytotoxic chemotherapy, and broad-spectrum antibiotics. Candida tropicalis is a pathogenic Candida species associated with considerable morbidity, mortality, and drug resistance issues on a global scale.

Methodology: 

We report a case of a 43-year-old man who was admitted to our hospital for further management of severe coronavirus disease 2019 (COVID-19) pneumonia. During his stay in the ward, he received systemic corticosteroids for a total duration of 32 days. A broad-spectrum antibiotic (piperacillin-tazobactam) was also given due to copious amounts of tracheostomy secretions.

Results: 

The patient’s fever recurred following an afebrile interval of 11 days, and C. tropicalis was cultured from his blood. The yeast was highly resistant to fluconazole and voriconazole but remained susceptible to echinocandins. Unfortunately, the patient was unable to receive any echinocandin and eventually succumbed to candidemia.

Conclusions: 

Multilocus sequence typing was used to characterize C. tropicalis as a novel diploid sequence type (i.e., 1515) that has not been previously reported.

Source: Journal of Infection in Developing Countries, https://www.jidc.org/index.php/journal/article/view/39863954

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