![]() ![]() ![]() ![]() RNA viruses represent a large and heterogeneous group of human pathogens that periodically jeopardize the public health because of apparent sudden epidemic outbreaks. Moreover, we highlight the most promising inhibitors of these proteins reported so far, including the possible strategies for their further development. Herein, we provide an exhaustive comparative analysis of SARS-CoV-2 proteases and RdRp with respect to other coronavirus homologues. Coronaviruses also possess a papain-like protease, another essential enzyme, still poorly characterized and not equally conserved, limiting the identification of broad-spectrum agents. The 3C-like (or Main) protease (3CL pro) and the nsp12 RNA-dependent RNA-polymerase (RdRp) are the best characterized SARS-CoV-2 targets and show the highest degree of conservation across coronaviruses fostering the identification of broad-spectrum inhibitors. Direct-acting agents, targeting protease and polymerase functionalities, represent a milestone in antiviral therapy. The identification of drugs to treat COVID-19 and other coronavirus diseases is an urgent global need, thus different strategies targeting either virus or host cell are still under investigation. The newly emerged coronavirus, called SARS-CoV-2, is the causing pathogen of pandemic COVID-19. ![]()
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