Potential Target for Drug of SARS-CoV-2

Cloud-Clone Corp.

The outbreak of Corvid 19 leads to more than two millions patients in the world. Researchers from various countries had done extensive work in studying the mechanism of virus infection, screening of effective drugs and searching for potential targets for new drugs. Previously studies showed that the invasion of the virus depends on ACES, CD147 and TMPRSS2.

In March, A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug Repurposing was jointly researched and published on Biorxiv by researchers from the United States, Britain and France.

By analyzing the genome of SARS-CoV-2, 28 viral proteins were cloned and expressed, including 4 structural proteins (S, M, N, E), 15 non-structural proteins forming the replicase / transcriptase complex (Nsp1, 2, 4-15 and Mutants of NSP5) and 9 putative accessory factors (Orf3a, 3b, 6, 7a, 7b, 8, 9b, 9c, 10). Then, affinity purification-mass spectrometry analysis identified 332 protein interactions between SARS-CoV-2 proteins and human proteins. Moreover, it was found that viral proteins are related to various biological processes, including protein trafficking, translation, transcription, and ubiquitination regulation.

After that, through chemoinformatics databases and analyses (Methods), of the 332 human targets that interact with the viral bait proteins with high significance, 62 have drugs/INDs/preclinical molecules that modulate them. Researchers are currently evaluating for efficacy of these molecules in live SARS-CoV-2 infection assays. At the same time, it is hoped that the analysis in this paper will provide important molecular targets for the development of broadly effective antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains (Table 1).

Figure 1. Interactome of SARS-CoV-2 protein with human protein 1.

In April, Italian researchers published the article Master Regulator Analysis of the SARS-CoV-2/Human Interactome in the Journal of Clinical Medicine. Based on the current knowledge of the interactome between SARS-CoV-2 and host cell proteins, they performed Master Regulator Analysis to detect which parts of the human interactome are most affected by the infection. And the result showed that apoptotic, mitochondrial mechanisms and a downregulation of the ACE2 protein receptor were most affected. Targets in these pathways could be used to develop specific therapies against the new virus (Table 2).

Figure 2. Interactome map of SARS-CoV-2 protein with human protein2.

Reference:

1. https://www.biorxiv.org/content/10.1101/2020.03.22.002386v3.full

2. https://www.mdpi.com/2077-0383/9/4/982/htm




Table 1. Human targets interact with SARS-CoV-2 proteins 1.

<table cellspacing="0" 85" valign="bottom" nowrap="">

Target Name

Catalog No.

Target Name

Catalog No.

Target Name

Catalog No.

Target Name

Catalog No.

AASS

C855

ETFA

E527

MFGE8

B286

PTGES2

A905

AATF

A440

EXOSC2

H822

MIB1

L727

PVR

B550

ACADM

D662

F2RL1

A852

MOGS

D185

RAB1A

J783

ACSL3

D673

FBLN5

D153

MTARC1

R574

RALA

M097

ADAM9

B829

FBN1

A593

NARS2

G132

RBX1

G674

ADAMTS1

B973

FBN2

A368

NEU1

B611

RDX

C774

ANO6

F813

FKBP10

E680

NIN

C657

RHOA

E320

AP2M1

G107

FKBP7

E677

NPC2

L139

RIPK1

E640

AP3B1

G109

GDF15

C034

NPTX1

A298

SDF2

A477

ATP13A3

N361

GGH

J038

NUP210

B421

SIRT5

E915

BAG5

F225

GHITM

B208

NUP62

C257

SLC44A2

E514

BRD2

F132

GLA

A183

NUP88

B198

STC2

F913

CENPF

A347

GPX1

A295

NUP98

B196

STOML2

F917

CNTRL

C373

HMOX1

A584

NUTF2

C671

TARS2

G136

COL6A1

C150

HS2ST1

H881

OS9

C693

TBCA

C784

COMT

J365

HYOU1

C537

PCNT

C716

TBK1

H061

CRTC3

E001

IDE

B897

PITRM1

B473

TIMM8B

P581

CSDE1

M893

IL17RA

B644

PKP2

A445

TOMM70

P574

CUL2

F362

IMPDH2

F632

PLAT

A525

TOR1A

G631

DNMT1

J244

INHBE

A048

PLOD2

E257

UBAP2

E593

EIF4H

F019

ITGB1

B042

POFUT1

C072

UGGT2

J268

ELOB

D968

LMAN2

H730

POLA1

C713

WFS1

L118

ELOC

D969

LOX

C580

POR

D312



ERP44

F404

MAT2B

G468

PSMD8

P778




Table 2. Human targets interact with SARS-CoV-2 proteins 2.

Target Name

Catalog No.

Target Name

Catalog No.

Target Name

Catalog No.

Target Name

Catalog No.

EEF1A1

F020

TMPRSS2

C795

SERPING1

A235

ALB

B028

RNF128

E936

ENO1

B449

XPA

E744

NMB

A803

DCTN2

C897

UBE2I

E600

LCP1

C561

DDAH2

D981

ACE2

B886

BCL2L1

E582

COX2

D284

TPSAB1

B070

SFTPD

B039

CHEK2

P087

TBCB

E725

FKBP1A

E641

OCIAD2

R870

IKBKB

J822

BAT3

J947

BCL2

A778

BCL2L2

L251

NAE1

C219

TPSB2

D781

HGS

H912

CAV1

A214

ISLR

H781

HNRPA1

C252

KPNA2

E748

CAMLG

C356

CD209

B614

CLEC4M

B730

DDX5

L418

PPIA

A979

TERF1

C788

IRF3

B589

MCL1

C615

PFDN5

E738

SMOC1

N564

BCL2A1

L252