tetano
Editor, Senior Moderator
J Infect Public Health
. 2023 May 10;16(7):1048-1056.
doi: 10.1016/j.jiph.2023.05.010. Online ahead of print. Revealing the structural and molecular interaction landscape of the favipiravir-RTP and SARS-CoV-2 RdRp complex through integrative bioinformatics: Insights for developing potent drugs targeting SARS-CoV-2 and other viruses
Chiranjib Chakraborty[SUP] 1 [/SUP], Manojit Bhattacharya[SUP] 2 [/SUP], Abinit Saha[SUP] 3 [/SUP], Abdulrahman Alshammari[SUP] 4 [/SUP], Metab Alharbi[SUP] 4 [/SUP], G Saikumar[SUP] 5 [/SUP], Soumen Pal[SUP] 6 [/SUP], Kuldeep Dhama[SUP] 5 [/SUP], Sang-Soo Lee[SUP] 7 [/SUP]
Affiliations
Background: The global research community has made considerable progress in therapeutic and vaccine research during the COVID-19 pandemic. Several therapeutics have been repurposed for the treatment of COVID-19. One such compound is, favipiravir, which was approved for the treatment of influenza viruses, including drug-resistant influenza. Despite the limited information on its molecular activity, clinical trials have attempted to determine the effectiveness of favipiravir in patients with mild to moderate COVID-19. Here, we report the structural and molecular interaction landscape of the macromolecular complex of favipiravir-RTP and SARS-CoV-2 RdRp with the RNA chain.
Methods: Integrative bioinformatics was used to reveal the structural and molecular interaction landscapes of two macromolecular complexes retrieved from RCSB PDB.
Results: We analyzed the interactive residues, H-bonds, and interaction interfaces to evaluate the structural and molecular interaction landscapes of the two macromolecular complexes. We found seven and six H-bonds in the first and second interaction landscapes, respectively. The maximum bond length is 3.79 Å. In the hydrophobic interactions, five residues (Asp618, Asp760, Thr687, Asp623, and Val557) were associated with the first complex and two residues (Lys73 and Tyr217) were associated with the second complex. The mobilities, collective motion, and B-factor of the two macromolecular complexes were analyzed. Finally, we developed different models, including trees, clusters, and heat maps of antiviral molecules, to evaluate the therapeutic status of favipiravir as an antiviral drug.
Conclusions: The results revealed the structural and molecular interaction landscape of the binding mode of favipiravir with the nsp7-nsp8-nsp12-RNA SARS-CoV-2 RdRp complex. Our findings can help future researchers in understanding the mechanism underlying viral action and guide the design of nucleotide analogs that mimic favipiravir and exhibit greater potency as antiviral drugs against SARS-CoV-2 and other infectious viruses. Thus, our work can help in preparing for future epidemics and pandemics.
Keywords: Favipiravir-RTP; RdRp complex; SARS-CoV-2; Structural and molecular interaction.
. 2023 May 10;16(7):1048-1056.
doi: 10.1016/j.jiph.2023.05.010. Online ahead of print. Revealing the structural and molecular interaction landscape of the favipiravir-RTP and SARS-CoV-2 RdRp complex through integrative bioinformatics: Insights for developing potent drugs targeting SARS-CoV-2 and other viruses
Chiranjib Chakraborty[SUP] 1 [/SUP], Manojit Bhattacharya[SUP] 2 [/SUP], Abinit Saha[SUP] 3 [/SUP], Abdulrahman Alshammari[SUP] 4 [/SUP], Metab Alharbi[SUP] 4 [/SUP], G Saikumar[SUP] 5 [/SUP], Soumen Pal[SUP] 6 [/SUP], Kuldeep Dhama[SUP] 5 [/SUP], Sang-Soo Lee[SUP] 7 [/SUP]
Affiliations
- PMID: 37196368
- DOI: 10.1016/j.jiph.2023.05.010
Background: The global research community has made considerable progress in therapeutic and vaccine research during the COVID-19 pandemic. Several therapeutics have been repurposed for the treatment of COVID-19. One such compound is, favipiravir, which was approved for the treatment of influenza viruses, including drug-resistant influenza. Despite the limited information on its molecular activity, clinical trials have attempted to determine the effectiveness of favipiravir in patients with mild to moderate COVID-19. Here, we report the structural and molecular interaction landscape of the macromolecular complex of favipiravir-RTP and SARS-CoV-2 RdRp with the RNA chain.
Methods: Integrative bioinformatics was used to reveal the structural and molecular interaction landscapes of two macromolecular complexes retrieved from RCSB PDB.
Results: We analyzed the interactive residues, H-bonds, and interaction interfaces to evaluate the structural and molecular interaction landscapes of the two macromolecular complexes. We found seven and six H-bonds in the first and second interaction landscapes, respectively. The maximum bond length is 3.79 Å. In the hydrophobic interactions, five residues (Asp618, Asp760, Thr687, Asp623, and Val557) were associated with the first complex and two residues (Lys73 and Tyr217) were associated with the second complex. The mobilities, collective motion, and B-factor of the two macromolecular complexes were analyzed. Finally, we developed different models, including trees, clusters, and heat maps of antiviral molecules, to evaluate the therapeutic status of favipiravir as an antiviral drug.
Conclusions: The results revealed the structural and molecular interaction landscape of the binding mode of favipiravir with the nsp7-nsp8-nsp12-RNA SARS-CoV-2 RdRp complex. Our findings can help future researchers in understanding the mechanism underlying viral action and guide the design of nucleotide analogs that mimic favipiravir and exhibit greater potency as antiviral drugs against SARS-CoV-2 and other infectious viruses. Thus, our work can help in preparing for future epidemics and pandemics.
Keywords: Favipiravir-RTP; RdRp complex; SARS-CoV-2; Structural and molecular interaction.