Screening of FDA-approved compound library identifies potential small-molecule inhibitors of SARS-CoV-2 non-structural proteins NSP1, NSP4, NSP6 and NSP13: molecular modeling and molecular dynamics studies

Sundar, Shobana; Thangamani, Lokesh; Shanmughavel, P.; Rahul, C.N.; Aiswarya, Natarajan; Sekar, K.; Natarajan, Jeyakumar

doi:10.1007/s42485-021-00067-w

Cited by 15 publications

(11 citation statements)

References 34 publications

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“…Apart from structural proteins, SARS-CoV-2 encodes several nonstructural proteins (NSP1 to NSP16) that are also known to play various important functions . Several studies have utilized MD simulations to investigate the effect and binding modes of approved and repurposed drugs, natural bioactive and metabolite molecules, and inhibitors against NSPs. − However, as they are at the early stages of possible therapeutics development, it is outside the scope of the present perspective to discuss them in detail.…”

Section: Protein Interactions and Conformational Dynamicsmentioning

confidence: 99%

Accelerating COVID-19 Research Using Molecular Dynamics Simulation

2021

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The COVID-19 pandemic has emerged as a global medico-socio-economic disaster. Given the lack of effective therapeutics against SARS-CoV-2, scientists are racing to disseminate suggestions for rapidly deployable therapeutic options, including drug repurposing and repositioning strategies. Molecular dynamics (MD) simulations have provided the opportunity to make rational scientific breakthroughs in a time of crisis. Advancements in these technologies in recent years have become an indispensable tool for scientists studying protein structure, function, dynamics, interactions, and drug discovery. Integrating the structural data obtained from high-resolution methods with MD simulations has helped in comprehending the process of infection and pathogenesis, as well as the SARS-CoV-2 maturation in host cells, in a short duration of time. It has also guided us to identify and prioritize drug targets and new chemical entities, and to repurpose drugs. Here, we discuss how MD simulation has been explored by the scientific community to accelerate and guide translational research on SARS-CoV-2 in the past year. We have also considered future research directions for researchers, where MD simulations can help fill the existing gaps in COVID-19 research.

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Section: Protein Interactions and Conformational Dynamicsmentioning

confidence: 99%

Accelerating COVID-19 Research Using Molecular Dynamics Simulation

2021

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“… 1146 repurposed 291 drugs to Mpro and PLpro. More similar works include refs ( 599 , 609 , 622 , 624 , 628 , 632 , 637 , 838 , 875 , 889 , and 1147 − 1173 ).…”

Section: Methods and Approachesmentioning

confidence: 99%

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

Gao¹,

Wang²,

Chen³

et al. 2022

Chem. Rev.

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Despite tremendous efforts in the past two years, our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), virus–host interactions, immune response, virulence, transmission, and evolution is still very limited. This limitation calls for further in-depth investigation. Computational studies have become an indispensable component in combating coronavirus disease 2019 (COVID-19) due to their low cost, their efficiency, and the fact that they are free from safety and ethical constraints. Additionally, the mechanism that governs the global evolution and transmission of SARS-CoV-2 cannot be revealed from individual experiments and was discovered by integrating genotyping of massive viral sequences, biophysical modeling of protein–protein interactions, deep mutational data, deep learning, and advanced mathematics. There exists a tsunami of literature on the molecular modeling, simulations, and predictions of SARS-CoV-2 and related developments of drugs, vaccines, antibodies, and diagnostics. To provide readers with a quick update about this literature, we present a comprehensive and systematic methodology-centered review. Aspects such as molecular biophysics, bioinformatics, cheminformatics, machine learning, and mathematics are discussed. This review will be beneficial to researchers who are looking for ways to contribute to SARS-CoV-2 studies and those who are interested in the status of the field.

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“…An ER-localized transmembrane protein (as nsp3 and nsp6), is considered to be involved in the assembly of virus-induced cytoplasmic double-membrane vesicles [168]. Participates in the RTC formation [167].…”

Section: Nsp4mentioning

confidence: 99%

SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19

Gusev

Sarapultsev

Соломатина

et al. 2022

IJMS

130

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The review aims to consolidate research findings on the molecular mechanisms and virulence and pathogenicity characteristics of coronavirus disease (COVID-19) causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and their relevance to four typical stages in the development of acute viral infection. These four stages are invasion; primary blockade of antiviral innate immunity; engagement of the virus’s protection mechanisms against the factors of adaptive immunity; and acute, long-term complications of COVID-19. The invasion stage entails the recognition of the spike protein (S) of SARS-CoV-2 target cell receptors, namely, the main receptor (angiotensin-converting enzyme 2, ACE2), its coreceptors, and potential alternative receptors. The presence of a diverse repertoire of receptors allows SARS-CoV-2 to infect various types of cells, including those not expressing ACE2. During the second stage, the majority of the polyfunctional structural, non-structural, and extra proteins SARS-CoV-2 synthesizes in infected cells are involved in the primary blockage of antiviral innate immunity. A high degree of redundancy and systemic action characterizing these pathogenic factors allows SARS-CoV-2 to overcome antiviral mechanisms at the initial stages of invasion. The third stage includes passive and active protection of the virus from factors of adaptive immunity, overcoming of the barrier function at the focus of inflammation, and generalization of SARS-CoV-2 in the body. The fourth stage is associated with the deployment of variants of acute and long-term complications of COVID-19. SARS-CoV-2’s ability to induce autoimmune and autoinflammatory pathways of tissue invasion and development of both immunosuppressive and hyperergic mechanisms of systemic inflammation is critical at this stage of infection.

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Screening of FDA-approved compound library identifies potential small-molecule inhibitors of SARS-CoV-2 non-structural proteins NSP1, NSP4, NSP6 and NSP13: molecular modeling and molecular dynamics studies

Cited by 15 publications

References 34 publications

Accelerating COVID-19 Research Using Molecular Dynamics Simulation

Accelerating COVID-19 Research Using Molecular Dynamics Simulation

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19

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