Coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 helicase inhibitors: a systematic review of in vitro studies

Mehyar, Nimer

doi:10.1016/j.jve.2023.100327

Cited by 5 publications

(7 citation statements)

References 110 publications

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“…32 In this study, we further explored metal-based antivirals for combating SARS-CoV-2 infection. Despite nsp13 being considered as a perfect drug target for the development of antivirals against SARS-CoV and SARS-CoV-2 according to previous reports, 15,16,36,40–43 it is unknown whether these inhibitors targeted nsp13 in virus-infected mammalian cells. Herein, we validated for the first time that nsp13 is a target of bismuth-based antivirals using an enrichment strategy based on our previous report.…”

Section: Discussionmentioning

confidence: 99%

Mechanistic insights into bismuth(iii) inhibition of SARS-CoV-2 helicase

Wei,

Chan,

Zhou

et al. 2024

Chem. Sci.

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Section: Discussionmentioning

confidence: 99%

Mechanistic insights into bismuth(iii) inhibition of SARS-CoV-2 helicase

Wei,

Chan,

Zhou

et al. 2024

Chem. Sci.

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“…Over the last several years, several putative inhibitors of different coronavirus Nsp13s have been reported to function both in vitro and in cells . Most of these compounds are high-nanomolar to mid-micromolar inhibitors of helicase activity.…”

Section: Discussionmentioning

confidence: 99%

“…8 Hence, helicases are putative targets for the development of broadly effective treatments for coronavirus-related illnesses. 9 Nsp13 is a Superfamily 1B (SF1B) helicase that is composed of five domains (Figure 1B). These domains consist of a zinc binding domain, which coordinates three Zn 2+ ions, as well as the structural stalk domain that is connected through the 1B domain to the 1A and 2A RecA-like core helicase subdomains.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Previous reports have shown that a small molecule inhibitor (SSYA10-001) of SARS-CoV-1 Nsp13 is able to block viral replication in host cells, and is also effective against MERS-CoV and a murine coronavirus called mouse hepatitis virus . Hence, helicases are putative targets for the development of broadly effective treatments for coronavirus-related illnesses …”

Section: Introductionmentioning

confidence: 99%

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A Repurposed Drug Interferes with Nucleic Acid to Inhibit the Dual Activities of Coronavirus Nsp13

Soper,

Yardumian,

Chen

et al. 2024

ACS Chem. Biol.

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The recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlighted a critical need to discover more effective antivirals. While therapeutics for SARS-CoV-2 exist, its nonstructural protein 13 (Nsp13) remains a clinically untapped target. Nsp13 is a helicase responsible for unwinding double-stranded RNA during viral replication and is essential for propagation. Like other helicases, Nsp13 has two active sites: a nucleotide binding site that hydrolyzes nucleoside triphosphates (NTPs) and a nucleic acid binding channel that unwinds double-stranded RNA or DNA. Targeting viral helicases with small molecules, as well as the identification of ligand binding pockets, have been ongoing challenges, partly due to the flexible nature of these proteins.Here, we use a virtual screen to identify ligands of Nsp13 from a collection of clinically used drugs. We find that a known ion channel inhibitor, IOWH-032, inhibits the dual ATPase and helicase activities of SARS-CoV-2 Nsp13 at low micromolar concentrations. Kinetic and binding assays, along with computational and mutational analyses, indicate that IOWH-032 interacts with the RNA binding interface, leading to displacement of nucleic acid substrate, but not bound ATP. Evaluation of IOWH-032 with microbial helicases from other superfamilies reveals that it is selective for coronavirus Nsp13. Furthermore, it remains active against mutants representative of observed SARS-CoV-2 variants. Overall, this work provides a new inhibitor for Nsp13 and provides a rationale for a recent observation that IOWH-032 lowers SARS-CoV-2 viral loads in human cells, setting the stage for the discovery of other potent viral helicase modulators.

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“…The virtual screening of natural products using the molecular docking method plays a crucial role in evaluating the inhibitory activity of these molecules against SARS-CoV-2. However, these findings should be validated through in vitro studies [23]. Power et al, (2022) [24] screened ten natural compounds through in silico studies and found favorable ADMET profiles for the in vitro evaluation of their activity against SARS-CoV-2.…”

Section: Introductionmentioning

confidence: 99%

Molecular Docking and ADME-TOX Profiling of Moringa oleifera Constituents against SARS-CoV-2

Souza,

Sousa

et al. 2023

ARM

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The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2019) etiological agent, which has a high contagiousness and is to blame for the outbreak of acute viral pneumonia, is the cause of the respiratory disease COVID-19. The use of natural products grew as an alternative treatment for various diseases due to the abundance of organic molecules with pharmacological properties. Many pharmaceutical studies have focused on investigating compounds with therapeutic potential. Therefore, this study aimed to identify potential antiviral compounds from a popular medicinal plant called Moringa oleifera Lam. against the spike, Mpro, ACE2, and RBD targets of SARS-CoV-2. For this, we use molecular docking to identify the molecules with the greatest affinity for the targets through the orientation of the ligand with the receptor in complex. For the best results, ADME-TOX predictions were performed to evaluate the pharmacokinetic properties of the compounds using the online tool pkCSM. The results demonstrate that among the 61 molecules of M. oleifera, 22 molecules showed promising inhibition results, where the compound ellagic acid showed significant molecular affinity (−9.3 kcal.mol−1) in interaction with the spike protein. These results highlight the relevance of investigating natural compounds from M. oleifera as potential antivirals against SARS-CoV-2; however, additional studies are needed to confirm the antiviral activity of the compounds.

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Coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 helicase inhibitors: a systematic review of in vitro studies

Cited by 5 publications

References 110 publications

Mechanistic insights into bismuth(iii) inhibition of SARS-CoV-2 helicase

Mechanistic insights into bismuth(iii) inhibition of SARS-CoV-2 helicase

A Repurposed Drug Interferes with Nucleic Acid to Inhibit the Dual Activities of Coronavirus Nsp13

Molecular Docking and ADME-TOX Profiling of Moringa oleifera Constituents against SARS-CoV-2

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