Zinc2+ ion inhibits SARS-CoV-2 main protease and viral replication in vitro.
Love Panchariya,Wajahat Ali Khan,Shobhan Kuila,Kirtishila Sonkar,Sibasis Sahoo,Archita Ghoshal,Ankit Kumar,Dileep Kumar Verma,Abdul Hasan,Mohd Azeem Khan,Niyati Jain,Amit Kumar Mohapatra,Shubhashis Das,Jitendra K. Thakur,Souvik Maiti,Souvik Maiti,Ranjan Kumar Nanda,Rajkumar Halder,Sujatha Sunil,A. Arockiasamy +19 more
TLDR
In this article, the first crystal structure of the Mpro-Zn2+ complex at 1.9 A was presented and provided the structural basis of viral replication inhibition, which showed that zinc not only inhibits the SARS-CoV-2 main protease (Mpro) with nanomolar affinity, but also viral replication.About:
This article is published in Chemical Communications.The article was published on 2021-09-30 and is currently open access. It has received 27 citations till now. The article focuses on the topics: Viral replication & Protease.read more
Citations
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Inhibition of the main protease of SARS-CoV-2 (Mpro) by repurposing/designing drug-like substances and utilizing nature’s toolbox of bioactive compounds
TL;DR: The main protease (Mpro) of the virus is an appealing target for the development of inhibitors, due to its importance in the viral life cycle and its high conservation among different coronaviruses as mentioned in this paper .
Journal ArticleDOI
Advances in the Development of SARS-CoV-2 Mpro Inhibitors
TL;DR: A huge effort was then carried out by the scientific community to design, synthesize and test new small molecules acting as inactivators of SARS-CoV-2 Mpro as mentioned in this paper .
Journal ArticleDOI
The Effect of Circulating Zinc, Selenium, Copper and Vitamin K1 on COVID-19 Outcomes: A Mendelian Randomization Study
TL;DR: In this article , the authors employed a two-sample Mendelian Randomization (MR) analysis to test whether genetically predicted zinc, selenium, copper and vitamin K1 levels have a causal effect on COVID-19 related outcomes, including risk of infection, hospitalization and critical illness.
Journal ArticleDOI
The temperature-dependent conformational ensemble of SARS-CoV-2 main protease (M<sup>pro</sup>)
TL;DR: In this paper , a series of high-resolution crystal structures of unliganded SARS-CoV-2 main protease, or Mpro, were obtained at different tem-per-atures from cryogenic to physiological.
Posted ContentDOI
The temperature-dependent conformational ensemble of SARS-CoV-2 main protease (M pro )
A. Ebrahim,Blake T. Riley,D. Kumaran,B. Andi,B. Andi,Martin Fuchs,S. McSweeney,S. McSweeney,Daniel A. Keedy,Daniel A. Keedy +9 more
TL;DR: X-ray crystallography at variable temperature for SARS-CoV-2 M pro reveals a complex conformational landscape, including mobile solvent at the catalytic dyad, mercurial conformational heterogeneity in a key substrate-binding loop, and an intramolecular network bridging the active site and dimer interface.
References
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A new coronavirus associated with human respiratory disease in China.
Fan Wu,Su Zhao,Bin Yu,Yan-Mei Chen,Wen Wang,Zhi gang Song,Yi Hu,Zhao Wu Tao,Jun Hua Tian,Yuan Yuan Pei,Ming Li Yuan,Yu Ling Zhang,Fa Hui Dai,Yi Liu,Qi Min Wang,Jiao Jiao Zheng,Lin Xu,Edward C. Holmes,Edward C. Holmes,Yong-Zhen Zhang,Yong-Zhen Zhang +20 more
TL;DR: Phylogenetic and metagenomic analyses of the complete viral genome of a new coronavirus from the family Coronaviridae reveal that the virus is closely related to a group of SARS-like coronaviruses found in bats in China.
Journal ArticleDOI
Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors
Zhenming Jin,Zhenming Jin,Xiaoyu Du,Yechun Xu,Yong-Qiang Deng,Meiqin Liu,Yao Zhao,Bing Zhang,Xiaofeng Li,Leike Zhang,Chao Peng,Yinkai Duan,Jing Yu,Lin Wang,Kailin Yang,Fengjiang Liu,Ren-Di Jiang,Xing-Lou Yang,Tian You,Liu X,Xiuna Yang,Fang Bai,Hong Liu,Xiang Liu,Luke W. Guddat,Wenqing Xu,Wenqing Xu,Gengfu Xiao,Cheng-Feng Qin,Zhengli Shi,Hualiang Jiang,Hualiang Jiang,Zihe Rao,Zihe Rao,Zihe Rao,Haitao Yang +35 more
TL;DR: A programme of structure-assisted drug design and high-throughput screening identifies six compounds that inhibit the main protease of SARS-CoV-2, demonstrating the ability of this strategy to isolate drug leads with clinical potential.
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Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors
Linlin Zhang,Daizong Lin,Xinyuanyuan Sun,Ute Curth,Christian Drosten,Lucie Sauerhering,Stephan Becker,Katharina Rox,Rolf Hilgenfeld +8 more
TL;DR: The pharmacokinetic characterization of the optimized inhibitor reveals a pronounced lung tropism and suitability for administration by the inhalative route and work that may provide a basis for development of anticoronaviral drugs.
Journal ArticleDOI
Zn2+ inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture
Aartjan J. W. te Velthuis,Sjoerd H. E. van den Worm,Amy C. Sims,Ralph S. Baric,Eric J. Snijder,Martijn J. van Hemert +5 more
TL;DR: It is demonstrated that the combination of Zn2+ and PT at low concentrations reduces the replication of SARS-coronavirus (SARS-CoV) and equine arteritis virus (EAV) in cell culture and efficiently inhibits the RNA-synthesizing activity of the RTCs of both viruses.
Journal ArticleDOI
Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease.
Chunlong Ma,Michael Dominic Sacco,Brett L. Hurst,Julia Alma Townsend,Yanmei Hu,Tommy Szeto,Xiujun Zhang,Bart Tarbet,Michael T. Marty,Yu Chen,Jun Wang +10 more
TL;DR: This study reports the discovery of inhibitors targeting the SARS-CoV-2 main protease (M pro) using the FRET-based enzymatic assay, and indicates that boceprevir, GC-376, and calpain inhibitors II, and XII represent novel chemotypes that are distinct from known substrate-based peptidomimetic M pro inhibitors.