Is PF-00835231 a Pan-SARS-CoV-2 Mpro Inhibitor? A Comparative Study

被引：20

作者：

Baig, Mohammad Hassan ^{[1
]}

Sharma, Tanuj ^{[1
]}

Ahmad, Irfan ^{[2
]}

Abohashrh, Mohammed ^{[3
]}

Alam, Mohammad Mahtab ^{[3
]}

Dong, Jae-June ^{[1
]}

机构：

[1] Yonsei Univ, Dept Family Med, Coll Med, 50-1 Yonsei Ro, Seoul 120752, South Korea

[2] King Khalid Univ, Coll Appl Med Sci, Dept Clin Lab Sci, Abha 61421, Saudi Arabia

[3] King Khalid Univ, Coll Appl Med Sci, Dept Basic Med Sci, Abha 61421, Saudi Arabia

来源：

MOLECULES | 2021年 / 26卷 / 06期

基金：

新加坡国家研究基金会;

关键词：

SARS-CoV-2; main protease; mutants; inhibitors; PF-00835231; MOLECULAR-DYNAMICS; PROTEIN MODELS; MAIN PROTEASE; IDENTIFICATION; SIMULATION;

D O I：

10.3390/molecules26061678

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The COVID-19 outbreak continues to spread worldwide at a rapid rate. Currently, the absence of any effective antiviral treatment is the major concern for the global population. The reports of the occurrence of various point mutations within the important therapeutic target protein of SARS-CoV-2 has elevated the problem. The SARS-CoV-2 main protease (Mpro) is a major therapeutic target for new antiviral designs. In this study, the efficacy of PF-00835231 was investigated (a Mpro inhibitor under clinical trials) against the Mpro and their reported mutants. Various in silico approaches were used to investigate and compare the efficacy of PF-00835231 and five drugs previously documented to inhibit the Mpro. Our study shows that PF-00835231 is not only effective against the wild type but demonstrates a high affinity against the studied mutants as well.

引用

页数：12

共 54 条

[1]

Analytica O, 2022, Emerald Expert Briefings, DOI [10.1108/OXAN-DB270270, DOI 10.1108/OXAN-DB270270]

[2] In-silico drug repurposing study predicts the combination of pirfenidone and melatonin as a promising candidate therapy to reduce SARS-CoV-2 infection progression and respiratory distress caused by cytokine storm [J].

Artigas, Laura ;

Coma, Mireia ;

Matos-Filipe, Pedro ;

Aguirre-Plans, Joaquim ;

Farres, Judith ;

Valls, Raquel ;

Fernandez-Fuentes, Narcis ;

de la Haba-Rodriguez, Juan ;

Olvera, Alex ;

Barbera, Jose ;

Morales, Rafael ;

Oliva, Baldo ;

Mas, Jose Manuel .

PLOS ONE, 2020, 15 (10)

[3] Discover potential inhibitors for PFKFB3 using 3D-QSAR, virtual screening, molecular docking and molecular dynamics simulation [J].

Bao, Yinfeng ;

Zhou, Lu ;

Dai, Duoqian ;

Zhu, Xiaohong ;

Hu, Yanqiu ;

Qiu, Yaping .

JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION, 2018, 38 (5-6) :413-431

[4] Identification of saquinavir as a potent inhibitor of dimeric SARS-CoV2 main protease through MM/GBSA [J].

Bello, Martiniano ;

Martinez-Munoz, Alberto ;

Balbuena-Rebolledo, Irving .

JOURNAL OF MOLECULAR MODELING, 2020, 26 (12)

[5] MOLECULAR-DYNAMICS WITH COUPLING TO AN EXTERNAL BATH [J].

BERENDSEN, HJC ;

POSTMA, JPM ;

VANGUNSTEREN, WF ;

DINOLA, A ;

HAAK, JR .

JOURNAL OF CHEMICAL PHYSICS, 1984, 81 (08) :3684-3690

[6]

Boras Britton, 2021, bioRxiv, DOI 10.1101/2020.09.12.293498

[7] A METHOD TO IDENTIFY PROTEIN SEQUENCES THAT FOLD INTO A KNOWN 3-DIMENSIONAL STRUCTURE [J].

BOWIE, JU ;

LUTHY, R ;

EISENBERG, D .

SCIENCE, 1991, 253 (5016) :164-170

[8]

Callaway E, 2020, NATURE, V585, DOI 10.1038/d41586-020-02544-6

[9] The GROMOS software for biomolecular simulation:: GROMOS05 [J].

Christen, M ;

Hünenberger, PH ;

Bakowies, D ;

Baron, R ;

Bürgi, R ;

Geerke, DP ;

Heinz, TN ;

Kastenholz, MA ;

Kräutler, V ;

Oostenbrink, C ;

Peter, C ;

Trzesniak, D ;

Van Gunsteren, WF .

JOURNAL OF COMPUTATIONAL CHEMISTRY, 2005, 26 (16) :1719-1751

[10] VERIFICATION OF PROTEIN STRUCTURES - PATTERNS OF NONBONDED ATOMIC INTERACTIONS [J].

COLOVOS, C ;

YEATES, TO .

PROTEIN SCIENCE, 1993, 2 (09) :1511-1519

← 1 2 3 4 5 6 →