Post #260 is misleading. Remdesivir is mainly polymerase inhibition rather than protease inhibition. It was confused for SARS-CoV 3CL protease due to our entry at post #249: 'coronavirus RdRp and 3CLpro showed a specific affinity to the homologous enzymes of plant potyviruses.' The confusion arose due to potyviral helper component protease, which carries an arginine-to-isoleucine mutation:
Jan 2020 Potyviral Helper Component Protease
A Double Mutation in the Conserved Motifs of the Helper Component Protease of Papaya Leaf Distortion Mosaic Virus for the Generation of a Cross-Pro... - PubMed - NCBI
SARS CoV 3CLpro
Inhibition of SARS-CoV 3CL protease by flavonoids. - PubMed - NCBI
Sept 2019 Remdesivir / RdRp (RNA-dependent RNA polymerase)
Remdesivir was originally called GS-5734
Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. - PubMed - NCBI
'....Clinical development of effective CoV-specific direct acting antivirals (DAAs) have been elusive even though there are several conserved druggable CoV enzyme targets including 3CL protease, PL protease, and NSP12 replicase. In 2016, Warren, et al, reported the in vivo antiviral efficacy of a small molecule monophosphoramide prodrug of an adenosine analogue, GS-5734 against ebola virus in non-human primates....RdRp-targeting therapies like GS-5734 are more likely to be broadly active against past, current, and future CoV due to inherent genetic conservation of the CoV replicase. These data suggest that GS-5734 can inhibit a broad range of diverse CoV including circulating, human, zoonotic, bat CoV, and prepandemic zoonotic CoV.'
Jan 2020 Potyviral Helper Component Protease
A Double Mutation in the Conserved Motifs of the Helper Component Protease of Papaya Leaf Distortion Mosaic Virus for the Generation of a Cross-Pro... - PubMed - NCBI
SARS CoV 3CLpro
Inhibition of SARS-CoV 3CL protease by flavonoids. - PubMed - NCBI
Sept 2019 Remdesivir / RdRp (RNA-dependent RNA polymerase)
Remdesivir was originally called GS-5734
Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. - PubMed - NCBI
'....Clinical development of effective CoV-specific direct acting antivirals (DAAs) have been elusive even though there are several conserved druggable CoV enzyme targets including 3CL protease, PL protease, and NSP12 replicase. In 2016, Warren, et al, reported the in vivo antiviral efficacy of a small molecule monophosphoramide prodrug of an adenosine analogue, GS-5734 against ebola virus in non-human primates....RdRp-targeting therapies like GS-5734 are more likely to be broadly active against past, current, and future CoV due to inherent genetic conservation of the CoV replicase. These data suggest that GS-5734 can inhibit a broad range of diverse CoV including circulating, human, zoonotic, bat CoV, and prepandemic zoonotic CoV.'
