Identification of Drugs Targeting Multiple Viral and Human Proteins Using Computational Analysis for Repurposing Against COVID-19

Sugandh Kumar, Pratima Kumari, Geetanjali Agnihotri, Preethy VijayKumar, Shaheerah Khan, Gulam Hussain Syed, Anshuman Dixit

10.26434/chemrxiv.12366938.v1

Research curated

Abstract

The SARS-CoV2 is a highly contagious pathogen that causes a respiratory disease named COVID-19. The COVID-19 was declared a pandemic by the WHO on 11th March 2020. It has affected about 5.38 million people globally (identified cases as on 24th May 2020), with an average lethality of ~3%. Unfortunately, there is no standard cure for the disease, although some drugs are under clinical trial. Thus, there is an urgent need of drugs for the treatment of COVID-19. The molecularly targeted therapies have proven their utility in various diseases such as HIV, SARS, and HCV. Therefore, a lot of efforts are being directed towards the identification of molecules that can be helpful in the management of COVID-19. In the current studies, we have used state of the art bioinformatics techniques to screen the FDA approved drugs against thirteen SARS-CoV2 proteins in order to identify drugs for quick repurposing. The strategy was to identify potential drugs that can target multiple viral proteins simultaneously. Our strategy originates from the fact that individual viral proteins play specific role in multiple aspects of viral lifecycle such as attachment, entry, replication, morphogenesis and egress and targeting them simultaneously will have better inhibitory effect. Additionally, we analyzed if the identified molecules can also affect the host proteins whose expression is differentially modulated during SARS-CoV2 infection. The differentially expressed genes (DEGs) were identified using analysis of NCBI-GEO data (GEO-ID: GSE-147507). A pathway and protein-protein interaction network analysis of the identified DEGs led to the identification of network hubs that may play important roles in SARS-CoV2 infection. Therefore, targeting such genes may also be a beneficial strategy to curb disease manifestation. We have identified 29 molecules that can bind to various SARS-CoV2 and human host proteins. We hope that this study will help researchers in the identification and repurposing of multipotent drugs, simultaneously targeting the several viral and host proteins, for the treatment of COVID-19.

Source: ChemRxiv

Related molecules

Name	Synonyms	Genes
nsp4	Non-structural protein 4
Octreotide	Octreotida, Octreotide, Octreotidum, Octrotide
Putative 2'-O-methyl transferase	2’-O-Ribose methyltransferase, Non-structural protein 16, Nonstructural protein 16, nsp16	rep, ORF1a-1b
Uridylate-specific endoribonuclease	NSP15, Non-structural protein 15, Nonstructural protein 15, NendoU, endoRNAse	rep, ORF1a-1b
Venetoclax
Helicase	Helicase, nsp13, Hel, p66, p66-HEL, Non-structural protein 13	rep, ORF1a-1b
Exoribonuclease	ExoN, Non-structural protein14, Nonstructural protein14, nsp14, 5‘-to-3‘ exonuclease	rep, ORF1a-1b
RNA dependent RNA polymerase	RDR, viral RNA polymerase, RdRp, nsp12	rep, ORF1a-1b, RdRp
Ribavirin	RBV, 1-beta-D-Ribofuranosyl-1,2,4-triazole-3-carboxamide, 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide
Cangrelor
Nebivolol
Pibrentasvir
Alatrofloxacin
Lapatinib
3C-like protease	3CLpro, Mpro, SARS coronavirus main peptidase, 3CLpro-SARS-CoV-2	rep, ORF1a-1b
Spike glycoprotein	Spike protein, S glycoprotein, S-Protein, S1, S2, S3, Peplomer protein, E2	S, ORF2
Capreomycin	Capastat
Nilotinib	Nilotinibum
nsp2	Non-structural protein 2
Desmopressin
Papain-like proteinases 1/2	Non-structural protein 3, papain like viral protease, nsp3, PL1-PRO/PL2-PRO, PLP1/PLP2, p195, Plpro	rep, ORF1a-1b
Indinavir

Related interactions

Target	Drug	Type	Result
Exoribonuclease	Cangrelor	Computational	positive
nsp2	Nilotinib	Computational	positive
Spike glycoprotein	Cangrelor	Computational	positive
Helicase	Cangrelor	Computational	positive
Exoribonuclease	Nilotinib	Computational	positive
nsp4	Lapatinib	Computational	positive
Helicase	Lapatinib	Computational	positive
Spike glycoprotein	Lapatinib	Computational	positive
Spike glycoprotein	Octreotide	Computational	positive
Helicase	Octreotide	Computational	positive
Putative 2'-O-methyl transferase	Octreotide	Computational	positive
Exoribonuclease	Nebivolol	Computational	positive
Papain-like proteinases 1/2	Nebivolol	Computational	positive
Putative 2'-O-methyl transferase	Ribavirin	Computational	positive
Papain-like proteinases 1/2	Ribavirin	Computational	positive
Papain-like proteinases 1/2	Desmopressin	Computational	positive
Uridylate-specific endoribonuclease	Desmopressin	Computational	positive
Helicase	Pibrentasvir	Computational	positive
RNA dependent RNA polymerase	Pibrentasvir	Computational	positive
Putative 2'-O-methyl transferase	Venetoclax	Computational	positive
Exoribonuclease	Venetoclax	Computational	positive
nsp2	Alatrofloxacin	Computational	positive
nsp4	Alatrofloxacin	Computational	positive
RNA dependent RNA polymerase	Indinavir	Computational	positive
3C-like protease	Indinavir	Computational	positive
3C-like protease	Cangrelor	Computational	positive
Putative 2'-O-methyl transferase	Capreomycin	Computational	positive
RNA dependent RNA polymerase	Capreomycin	Computational	positive