In silico studies of selected multi-drug targeting against 3CLpro and nsp12 RNA-dependent RNA-polymerase proteins of SARS-CoV-2 and SARS-CoV
Udofia et al.
, In silico studies of selected multi-drug targeting against 3CLpro and nsp12 RNA-dependent RNA-polymerase..
, Network Modeling Analysis in Health Informatics and Bioinformatics, doi:10.1007/s13721-021-00299-2
In Silico analysis finding that ivermectin had the highest binding energy against the 3CLpro of SARS-CoV-2 and RdRps of both SARS-CoV and SARS-CoV-2.
Udofia et al., 25 Mar 2021, peer-reviewed, 5 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: Network Modeling Analysis in Health Informatics and Bioinformatics (2021) 10:22
In silico studies of selected multi‑drug targeting against 3CLpro
and nsp12 RNA‑dependent RNA‑polymerase proteins of SARS‑CoV‑2
Inemesit A. Udofia1 · Kofoworola O. Gbayo1 · Oluwakemi A. Oloba‑Whenu1 · Taofeek B. Ogunbayo1 ·
Received: 31 October 2020 / Revised: 25 January 2021 / Accepted: 12 March 2021 / Published online: 25 March 2021
© The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature 2021
An outbreak of a cluster of viral pneumonia cases, subsequently identified as coronavirus disease 2019 (COVID-19), due to
a novel SARS-CoV-2 necessitates an urgent need for a vaccine to prevent infection or an approved medication for a cure. In
our in silico molecular docking study, a total of 173 compounds, including FDA-approved antiviral drugs, with good ADME
descriptors, and some other nucleotide analogues were screened. The results show that these compounds demonstrate strong
binding affinity for the residues at the active sites of RNA-dependent RNA-polymerase (RdRp) modelled structures and
Chymotrypsin-like cysteine protease (3CLpro) of the HCoV proteins. Free energies (ΔG’s) of binding for SARS-CoV-2
and SARS-CoV RdRp range from – 5.4 to – 8.8 kcal/mol and – 4.9 to – 8.7 kcal/mol, respectively. Also, SARS-CoV-2 and
SARS-CoV 3CLpro gave ΔG values ranging from − 5.1 to − 8.4 kcal/mol and − 5.5 to − 8.6 kcal/mol, respectively. Interesting results are obtained for ivermectin, an antiparasitic agent with broad spectrum activity, which gave the highest binding
energy value (− 8.8 kcal/mol) against the 3CLpro of SARS-CoV-2 and RdRps of both SARS-CoV and SARS-CoV-2. The
reason for such high binding energy values is probably due to the presence of hydroxy, methoxy and sugar moieties in its
structure. The stability of the protein–ligand complexes of polymerase inhibitors considered in this investigation, such as
Sofosbuvir, Remdesivir, Tenofovir, Ribavirin, Galidesivir, 5c3, 5h1 and 7a1, show strong to moderate hydrogen bonding
and hydrophobic interactions (π–π stacked, π–π T-shaped, π-sigma and π-alkyl). The stability provided from such interactions translate into greater antiviral activity or inhibitory effect of the ligands. Assessment of the average free energies of
binding of the FDA approved drugs are highly comparable for conformers of a particular inhibitor, indicating similar modes
of binding within the pockets.
Keywords COVID-19 · Molecular docking · Antiviral drugs · Binding energy · Ligand binding interaction
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