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Middle East respiratory syndrome coronavirus (MERS-CoV) is endemic in dromedary camels from the Arabian Peninsula and Africa; seroprevalence is >75% (1-3). Zoonotic transmission to humans has occurred sporadically, mainly on [...]

Zika virus (ZIKV), a member of the Flaviviridae family, is an important human pathogen that has caused epidemics in Africa, Southeast Asia, and the Americas. No licensed treatments for ZIKV disease are currently available. Favipiravir (T-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) and ribavirin (1-(β-D-Ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide) are nucleoside analogs that have exhibited antiviral activity against a broad spectrum of RNA viruses, including some flaviviruses. In this study, we strengthened evidence for favipiravir and ribavirin inhibition of ZIKV replication in vitro. Testing in IFNAR−/− mice revealed that daily treatments of favipiravir were sufficient to provide protection against lethal ZIKV challenge in a dose-dependent manner but did not completely abrogate disease. Ribavirin, on the other hand, had no beneficial effect against ZIKV infection in this model and under the conditions examined. Combined treatment of ribavirin and favipiravir did not show improved outcomes over ribavirin alone. Surprisingly, outcome of favipiravir treatment was sex-dependent, with 87% of female but only 25% of male mice surviving lethal ZIKV infection. Since virus mutations were not associated with outcome, a sex-specific host response likely explains the observed sex difference. [ABSTRACT FROM AUTHOR]

The occurrence of immune-evasive SARS-CoV-2 strains emphasizes the importance to search for broad-acting antiviral compounds. Our previous in vitro study showed that Pelargonium sidoides DC. root extract EPs ® 7630 has combined antiviral and immunomodulatory properties in SARS-CoV-2-infected human lung cells. Here we assessed in vivo effects of EPs ® 7630 in SARS-CoV-2-infected hamsters, and investigated properties of EPs ® 7630 and its functionally relevant constituents in context of phenotypically distinct SARS-CoV-2 variants. We show that EPs ® 7630 reduced viral load early in the course of infection and displayed significant immunomodulatory properties positively modulating disease progression in hamsters. In addition, we find that EPs ® 7630 differentially inhibits SARS-CoV-2 variants in nasal and bronchial human airway epithelial cells. Antiviral effects were more pronounced against Omicron BA.2 compared to B.1 and Delta, the latter two preferring TMPRSS2-mediated fusion with the plasma membrane for cell entry instead of receptor-mediated low pH-dependent endocytosis. By using SARS-CoV-2 Spike VSV-based pseudo particles (VSVpp), we confirm higher EPs ® 7630 activity against Omicron Spike-VSVpp, which seems independent of the serine protease TMPRSS2, suggesting that EPs ® 7630 targets endosomal entry. We identify at least two molecular constituents of EPs ® 7630, i.e., (-)-epigallocatechin and taxifolin with antiviral effects on SARS-CoV-2 replication and cell entry. In summary, our study shows that EPs ® 7630 ameliorates disease outcome in SARS-CoV-2-infected hamsters and has enhanced activity against Omicron, apparently by limiting late endosomal SARS-CoV-2 entry., Competing Interests: Authors ŽK and ML were employees by Dr. Willmar Schwabe GmbH and Co. KG. The funder had the following involvement with the study: ML contributed to the design of the study, analyzed data, provided material, wrote and edited the main text. ŽK provided material, analyzed data, wrote and edited the main text. SM and HP were employed by IDEXX Laboratories. AK was employed by Labor Dr. Krause und Kollegen MVZ GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Emanuel, Papies, Galander, Adler, Heinemann, Eschke, Merz, Pischon, Rose, Krumbholz, Kulić, Lehner, Trimpert and Müller.)