DEY, D.
In silico Studies Predict Efficient Binding of Remdesivir and Favipiravir with 3-chymotrypsin like protease of SARS-CoV-2 for COVID-19 Interventional Therapy - Vol.83(3), May-June - Mumbai Indian Journal of Pharmaceutical Science 2021 - 556-561p.
Favipiravir and remdesivir are investigational drugs for coronavirus disease 2019 that is caused by severe
acute respiratory syndrome coronavirus 2. The active forms of these drugs are reported to target and
inhibit viral RNA dependent RNA polymerase, which is derived from 3-chymotrypsin like protease, a viral
replicase enzyme. The present in silico study explores the comparative efficacy of these drugs to inhibit
3-chymotrypsin like protease and RNA dependent RNA polymerase, to plan therapeutic options for patients
based on their disease severity. Active favipiravir and remdesivir molecules bind to 3-chymotrypsin like
protease with energies of 6.18 and -6.52 kcal/mol in contrast to -5.62 and -3.91 kcal/mol for RNA dependent
RNA polymerase. Further, hydrophobic interactions and salt bridge formations cement drug bindings
with 3-chymotrypsin like protease, but not with RNA dependent RNA polymerase. Molecular dynamic
simulation experiments, performed under certain experimental constraints reveal that the root mean
square flexibilities of active residues in drug complexes with 3-chymotrypsin like protease are lower than
in free 3-chymotrypsin like protease making the former more stable than the latter because of their rigidity
and stabilities. Both drugs may hence serve as good therapeutic options for early stages of coronavirus
disease 2019. However, more severe symptoms may be treated better with favipiravir due to its better
binding with RNA dependent RNA polymerase, as compared to remdesivir. The “one drug does not fit all”
concept is true for coronavirus disease 2019 as it is being currently realized by clinicians all around the
world. Hence precise knowledge about critical interactions of these drugs with the viral enzymes will help
medicos make vital therapeutic decisions on interventional options for patients who report to hospitals
without over symptoms or with varying degrees of disease severity.
PHARMACEUTICS
In silico Studies Predict Efficient Binding of Remdesivir and Favipiravir with 3-chymotrypsin like protease of SARS-CoV-2 for COVID-19 Interventional Therapy - Vol.83(3), May-June - Mumbai Indian Journal of Pharmaceutical Science 2021 - 556-561p.
Favipiravir and remdesivir are investigational drugs for coronavirus disease 2019 that is caused by severe
acute respiratory syndrome coronavirus 2. The active forms of these drugs are reported to target and
inhibit viral RNA dependent RNA polymerase, which is derived from 3-chymotrypsin like protease, a viral
replicase enzyme. The present in silico study explores the comparative efficacy of these drugs to inhibit
3-chymotrypsin like protease and RNA dependent RNA polymerase, to plan therapeutic options for patients
based on their disease severity. Active favipiravir and remdesivir molecules bind to 3-chymotrypsin like
protease with energies of 6.18 and -6.52 kcal/mol in contrast to -5.62 and -3.91 kcal/mol for RNA dependent
RNA polymerase. Further, hydrophobic interactions and salt bridge formations cement drug bindings
with 3-chymotrypsin like protease, but not with RNA dependent RNA polymerase. Molecular dynamic
simulation experiments, performed under certain experimental constraints reveal that the root mean
square flexibilities of active residues in drug complexes with 3-chymotrypsin like protease are lower than
in free 3-chymotrypsin like protease making the former more stable than the latter because of their rigidity
and stabilities. Both drugs may hence serve as good therapeutic options for early stages of coronavirus
disease 2019. However, more severe symptoms may be treated better with favipiravir due to its better
binding with RNA dependent RNA polymerase, as compared to remdesivir. The “one drug does not fit all”
concept is true for coronavirus disease 2019 as it is being currently realized by clinicians all around the
world. Hence precise knowledge about critical interactions of these drugs with the viral enzymes will help
medicos make vital therapeutic decisions on interventional options for patients who report to hospitals
without over symptoms or with varying degrees of disease severity.
PHARMACEUTICS