![]() ![]() 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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