Abstract
In recent years, infectious diseases caused by viral infections have seriously endangered human health, especially COVID-19, caused by SARS-CoV-2, which continues to spread worldwide. The development of broad-spectrum antiviral inhibitors is urgently needed. Here, we report a series of small-molecule compounds that proved effective against human coronaviruses (HCoV), such as SARS-CoV-2 and its variants of concern (VOCs), including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529), SARS-CoV, MERS-CoV, HCoV-OC43, and other viruses with class I viral fusion proteins, such as influenza virus, Ebola virus (EBOV), Nipah virus (NiV), and Lassa fever virus (LASV). They are also effective against class II enveloped viruses represented by ZIKV and class III enveloped viruses represented by vesicular stomatitis virus (VSV). Further studies have shown that these compounds may exert antiviral effects through a variety of mechanisms, including inhibiting the formation of the six-helix bundle, which is a typical feature of enveloped virus fusion with cell membranes, and/or targeting viral membrane to inactivate cell-free virions. These compounds are expected to become drug candidates against SARS-CoV-2 and other enveloped viruses.
Highlights
In recent years, infectious diseases caused by viral infections have seriously endangered human health, especially COVID-19, caused by SARS-CoV-2, which continues to spread worldwide
Since the beginning of this century, infectious diseases caused by enveloped viruses, including severe acute respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2, as well as other enveloped viruses, such as influenza virus H1N1, Ebola virus (EBOV), and Zika virus (ZIKV), have severely affected human life and health [1–5]
Inhibitory and Inactivating Activity of FD001 and Analogs on Infection of SARS-CoV-2 and Previously, we found that FD001 acted as a fusion inhibitor against HIV-1 [16]
Summary
Infectious diseases caused by viral infections have seriously endangered human health, especially COVID-19, caused by SARS-CoV-2, which continues to spread worldwide. We report a series of small-molecule compounds that proved effective against human coronaviruses (HCoV), such as SARS-CoV-2 and its variants of concern (VOCs), including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529), SARS-CoV, MERS-CoV, HCoV-OC43, and other viruses with class I viral fusion proteins, such as influenza virus, Ebola virus (EBOV), Nipah virus (NiV), and Lassa fever virus (LASV). Further studies have shown that these compounds may exert antiviral effects through a variety of mechanisms, including inhibiting the formation of the six-helix bundle, which is a typical feature of enveloped virus fusion with cell membranes, and/or targeting viral membrane to inactivate cell-free virions These compounds are expected to become drug candidates against SARS-CoV-2 and other enveloped viruses. COVID-19, caused by SARS-CoV-2, is spreading rapidly around the world, and its impact on humans is unprecedented This pandemic has caused more than 373 million infections and 5.68 million deaths worldwide as of 30 January 2022 (https://www.who.int/emergencies/diseases/novel-coronavirus-2019). For COVID-19 treatment, the small-molecule compounds remdesivir [14] and molnupiravir [15] have been approved for clinical use by the US
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