![]() ![]() The open-label WHO Solidarity trial which included 2,750 persons randomized to remdesivir and 4,800 to standard-of-care detected no reduction in mortality, requirement for ventilation, or reduction in hospital stay for those receiving remdesivir ( 41). Finally, some nucleoside analogs are incorporated into viral genomes and inhibit replication by introducing mutations during subsequent rounds of virus replication. Others contain a 3′-hydroxyl group and yet still result in immediate or delayed chain termination. Most antiviral polymerase inhibitors lack a 3′-hydroxyl group and act as nucleoside analog chain terminators ( 12). For example, tenofovir and lamivudine are among the mainstays of therapy for treating human immunodeficiency virus and hepatitis B infections ( 12). Because of their broad spectrum of activity, nucleoside analog polymerase inhibitors have been the only successful repurposed directly acting antivirals. Nucleoside analog polymerase inhibitors are the most common antiviral compounds comprising a plurality of all licensed antivirals. RdRps are highly conserved in their structural and functional features, even among diverse RNA viruses belonging to different families ( 11). ![]() RNA-dependent RNA polymerases (RdRps) catalyze phosphodiester bond formation between nucleoside triphosphates in an RNA-templated manner.
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