Network analysis, sequence and structure dynamics of key proteins of coronavirus and human host, and molecular docking of selected phytochemicals of nine medicinal plants

Abstract

The novel coronavirus of 2019 (nCoV-19) has become a pandemic, affecting over 205 nations with over 7,410,000 confirmed cases which has resulted to over 418,000 deaths worldwide. This study aimed to identify potential therapeutic compounds and phytochemicals of medicinal plants that have potential to modulate the expression network of genes that are involve in SARS-CoV-2 pathology in human host and to understand the dynamics key proteins involved in the virus-host interactions. The method used include gene network analysis, molecular docking, and sequence and structure dynamics simulations. The results identified DNA-dependent protein kinase (DNA-PK) and Protein kinase CK2 as key players in SARS-CoV-2 lifecycle. Among the predicted drugs compounds, clemizole, monorden, spironolactone and tanespimycin showed high binding energies; among the studied repurposing compounds, remdesivir, simeprevir and valinomycin showed high binding energies; among the predicted acidic compounds, acetylursolic acid and hardwickiic acid gave high binding energies; while among the studied anthraquinones and glycosides compounds, ellagitannin and friedelanone showed high binding energies against 3-Chymotrypsin-like protease (3CL pro), Papain-like protease (PL pro), helicase (nsp13), RNA-dependent RNA polymerase (nsp12), 2'-O-ribose methyltransferase (nsp16) of SARS-CoV-2 and DNA-PK and CK2alpha in human. The order of affinity for CoV proteins is 5Y3E > 6NUS > 6JYT > 2XYR > 3VB6. Finally, medicinal plants with phytochemicals such as caffeine, ellagic acid, quercetin and their derivatives could possibly remediate COVID-19.

Hepatitis C Virus Protease Inhibitors Show Differential Efficacy and Interactions with Remdesivir for Treatment of SARS-CoV-2 in Vitro

“…The copyright holder for this this version posted December 2, 2020. ; https://doi.org/10.1101/2020.12.02.408112 doi: bioRxiv preprint binding of different HCV PI to SARS-CoV-2 M pro . [48][49][50][51][52][53][54][55][56][57][58][59][60][62][63][64][65][66][67][68]74 In several of these studies HCV PI were identified as top candidates following screening of large drug libraries, however, some of these studies also yielded contradictory results. Of these studies, 10 identified simeprevir 50,53,58,60,62,63,[65][66][67][68] , 5 paritaprevir 49,53,55,63,66 , 3 glecaprevir [54][55][56] , telaprevir 48,53,64 , boceprevir 48,57,59 and faldaprevir 48,60,…”

“…46 Finally, PI were suggested to affect innate immunity, as well as alternative viral targets, which could provide the basis for the observed differences in interactions with remdesivir. 48–68…”

“…Using in silico modelling approaches, at least 21 studies predicted binding of different HCV PI to SARS-CoV-2 M pro . 48–60,62–68,74 In several of these studies HCV PI were identified as top candidates following screening of large drug libraries, however, some of these studies also yielded contradictory results. Of these studies, 10 identified simeprevir 50,53,58,60,62,63,65–68 , 5 paritaprevir 49,53,55,63,66 , 3 glecaprevir 54–56 , telaprevir 48,53,64 , boceprevir 48,57,59 and faldaprevir 48,60,74 , 2 danoprevir 48,51 and asunaprevir 48,60 and 1 sovaprevir 48 , vaniprevir 48 , narlaparevir 48 and grazoprevir 52 to bind M pro .…”

The Nonribosomal Peptide Valinomycin: From Discovery to Bioactivity and Biosynthesis

“…In particular, valinomycin exhibits remarkable inhibitory effects on the viruses SARS-CoV and MERS-CoV, which share high genome similarity with SARS-CoV-2 that causes the current global pandemic of COVID-19. Moreover, molecular docking and dynamic simulations have shown that valinomycin shows high binding energies to SARS-CoV-2 proteins [ 61 ]. Therefore, valinomycin is a potential compound to be developed as a potent anti-SARS-CoV-2 agent to combat the ongoing, fast-spreading COVID-19 pandemic.…”

“…Notably, the amino acid sequences of the seven conserved replicase domains in ORF1ab that are used for CoV species classification are 94.4% identical between SARS-CoV-2 and SARS-CoV [ 60 ]. In addition, a recent study reported that valinomycin shows high binding energies towards SARS-CoV-2 proteins by molecular docking and dynamic simulations [ 61 ]. Therefore, valinomycin has the potential to be developed as a potent antiviral agent to combat the ongoing, fast-spreading global COVID-19 pandemic.…”