Hydroxychloroquine Inhibits Zika Virus NS2B-NS3 Protease

Kumar, Ankur; Liang, Brooke; Aarthy, Murali; Singh, Sanjeev Kumar; Garg, Neha; Mysorekar, Indira U.; Giri, Rajanish

doi:10.1021/acsomega.8b01002

Cited by 91 publications

(71 citation statements)

References 64 publications

(143 reference statements)

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“…Previous studies reported that CQ/HCQ possess a broad spectrum of antiv iral effects on a variety of viruses as diverse as human immunodeficiency virus (HIV) [30], Marburg virus, Zika virus [31], dengue virus [32], Ebola virus [33], and SARS-Co V-1 [34,35], etc. CQ and HCQ can interfere with the binding of viral particles to their cellular cell surface receptor or the pH-dependent endosome-med iated viral entry of enveloped viruses to inhibit the v iral cycle [32].…”

Section: Jak Inhibitorsmentioning

confidence: 99%

The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China

Zhang¹,

Zhao²,

Zhang³

et al. 2020

Clinical Immunology

1,158

1,316

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The pandemic outbreak of coronavirus disease 2019 is rap idly spreading all over the world. Reports from China showed that about 20% of patients developed severe disease, resulting in a fatality of 4%. In the past two months, we clinical immunologists participated in mu lti-rounds of MDT (mult idiscipline team) discussion on the anti-inflammat ion management of critical ill COVID-19 patients, with our colleagues dispatched from Ch inese leading PUM C Hospital to Wuhan to admit and treat the most severe patients . Here, fro m the perspective of clinical immunologists, we will discuss the clin ical and immunological characteristics of severe patients, and summarize the current evidence and share our experience in anti-inflammat ion treatment, including glucocorticoids, IL-6 antagonist, JAK inhibitors and choloroquine/hydrocholoroquine, of patients with severe COVID-19 that may have an impaired immune system.

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Section: Jak Inhibitorsmentioning

confidence: 99%

The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China

Zhang¹,

Zhao²,

Zhang³

et al. 2020

Clinical Immunology

1,158

1,316

View full text Add to dashboard Cite

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“…These vital functions of ZIKV helicase encourage to screen for antiviral molecules against its active sites. In a recent study, we have determine the inhibitory potential of a small molecule (HCQ) against ZIKV protease with computational and enzyme kinetics studies (30). Therefore, in this article, we have used molecular docking and simulation approach to find out a significant binding cavity for EGCG.…”

mentioning

confidence: 99%

Mechanistic insights into Zika virus NS3 helicase inhibition by Epigallocatechin-3-gallate

Kumar

Sharma

Aarthy

et al. 2019

Preprint

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Since 2007, repeated outbreaks of Zika virus (ZIKV) has affected millions of people worldwide and created global health concern with major complications like microcephaly and Guillain Barre's syndrome. Generally, ZIKV transmits through mosquitoes (Aedes aegypti) like other flaviviruses, but reports show blood transfusion and sexual mode of ZIKV transmission which further makes the situation alarming. Till date, there is not a single Zika specific licensed drug or vaccine present in the market. However, in recent months, several antiviral molecules have been screened against viral and host proteins.Among those, (−)-Epigallocatechin-3-gallate (EGCG), a green tea polyphenol has shown great virucidal potential against flaviviruses including ZIKV. However, the mechanistic understanding of EGCG targeting viral proteins is not yet entirely deciphered except little is known about its interaction with viral envelope protein and viral protease. Since literature has shown significant inhibitory interactions of EGCG against various kinases and bacterial DNA gyrases; we designed our study to find inhibitory actions of EGCG against ZIKV NS3 helicase. NS3 helicase is playing a significant role in viral replication by unwinding RNA after hydrolyzing NTP. We employed molecular docking and simulation approach and found significant interactions at ATPase site and also at RNA binding site. Further, the enzymatic assay has shown significant inhibition of NTPase activity with an IC50 value of 295.7 nM and Ki of 0.387 ± 0.034 µM. Our study suggests the possibility that EGCG could be considered as prime backbone molecule for further broadspectrum and multitargeted inhibitor development against ZIKV and other flaviviruses.author/funder. All rights reserved. No reuse allowed without permission.

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“…Chloroquine and hydroxychloroquine have been investigating for the treatment of SARS-CoV-2 (Devaux et al, 2020), and they have been reported to have direct antiviral effects, such as inhibition of flaviviruses, retroviruses (like HIV), and many coronaviruses. Additionally, Kumar et al (2018) reported that Hydroxychloroquine is capable of inhibiting Zika Virus' NS2B-NS3 Protease, and exhibited good viral replication blocking in infected JEG3 cells in concentration of 80 uM of Hydroxychloroquine. Furthermore, the use of chloroquine and its analogues can be corroborated by a recent study showing that, with EC50 of 1.13 µmol / L and SI greater than 88, chloroquine can effectively inhibit SARS-CoV-2 at the cellular level (Wang et al, 2020 b).…”

Section: Discussionmentioning

confidence: 99%

<strong>Computational Screening for Potential Drug Candidates Against SARS-CoV-2 Main Protease</strong>

Andrade¹,

Ghosh²,

Barh³

et al. 2020

Preprint

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Background: SARS-CoV-2 that are the causal agent of a current pandemic are enveloped, positive-sense, single-stranded RNA viruses of the Coronaviridae family. Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly and pathogenicity. The ~33.8KDa Mpro protease of SARS-CoV-2 is a non-human homologue and highly conserved among several coronaviruses indicating Mpro could be a potential drug target for Coronaviruses.Methods: Here we performed computational ligand screening of four pharmacophores (OEW, Remdesivir, Hydroxycholoquine and N3) that are presumed to have positive effects against SARS-CoV-2 Mpro protease (6LU7) and also screened 50,000 molecules from the ZINC Database dataset against this protease target.Results: We found 40 pharmacophore-like structures of natural compounds from diverse chemical classes that exhibited better affinity of docking as compared to the known ligands. The 10 best selected ligands namely, ZINC1845382, ZINC1875405, ZINC2092396, ZINC2104424, ZINC44018332, ZINC2101723, ZINC2094526, ZINC2094304, ZINC2104482, ZINC3984030, and ZINC1531664, are mainly classified as β-carboline, Alkaloids and Polyflavonoids, and all of them displayed interactions with dyad CYS145 and HIS41 from the protease pocket in a similar way as with other known ligands.Conclusion: Our results suggest that these 10 molecules could be effective against SARS-CoV-2 protease and may be tested in vitro and in vivo to develop novel drugs against this virus.

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Hydroxychloroquine Inhibits Zika Virus NS2B-NS3 Protease

Cited by 91 publications

References 64 publications

The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China

The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China

Mechanistic insights into Zika virus NS3 helicase inhibition by Epigallocatechin-3-gallate

<strong>Computational Screening for Potential Drug Candidates Against SARS-CoV-2 Main Protease</strong>

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