Genomic and structural mechanistic insight to reveal the differential infectivity of omicron and other variants of concern

Sharma, Priyanka; Kumar, Mukesh; Tripathi, Manish Kumar; Gupta, Deepali; Vishwakarma, Poorvi; Das, Uddipan; Kaur, Punit

doi:10.1016/j.compbiomed.2022.106129

Cited by 7 publications

(4 citation statements)

References 70 publications

(94 reference statements)

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“…In particular, the N501Y region, providing greater binding strength to the hACE2 receptor and the E484K region, is responsible for the decrease in the response by monoclonal antibodies. The combination of mutations that induce greater infectivity and immunological evasion makes P.1 more aggressive compared to other variants, as demonstrated in our results [68,69].…”

Section: Discussionsupporting

confidence: 70%

Virulence Profiles of Wild-Type, P.1 and Delta SARS-CoV-2 Variants in K18-hACE2 Transgenic Mice

Santos

Gamon

Azevedo

et al. 2023

Viruses

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Since December 2019, the world has been experiencing the COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and we now face the emergence of several variants. We aimed to assess the differences between the wild-type (Wt) (Wuhan) strain and the P.1 (Gamma) and Delta variants using infected K18-hACE2 mice. The clinical manifestations, behavior, virus load, pulmonary capacity, and histopathological alterations were analyzed. The P.1-infected mice showed weight loss and more severe clinical manifestations of COVID-19 than the Wt and Delta-infected mice. The respiratory capacity was reduced in the P.1-infected mice compared to the other groups. Pulmonary histological findings demonstrated that a more aggressive disease was generated by the P.1 and Delta variants compared to the Wt strain of the virus. The quantification of the SARS-CoV-2 viral copies varied greatly among the infected mice although it was higher in P.1-infected mice on the day of death. Our data revealed that K18-hACE2 mice infected with the P.1 variant develop a more severe infectious disease than those infected with the other variants, despite the significant heterogeneity among the mice.

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Section: Discussionsupporting

confidence: 70%

Virulence Profiles of Wild-Type, P.1 and Delta SARS-CoV-2 Variants in K18-hACE2 Transgenic Mice

Santos

Gamon

Azevedo

et al. 2023

Viruses

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“…(Schrodinger Suite, LLC, 2017-4; New York, NY, USA). Simultaneously, rotamer search methods, the VSGB solvent model, and the OPLS2005, force field were used to estimate the binding free energy and the ligand efficiency (ln values) using the equations as provided earlier ( Teng et al, 2021 , Sharma et al., 2022 ).…”

Section: Methodsmentioning

confidence: 99%

Drug repurposing approach against chikungunya virus: an in vitro and in silico study

Kasabe

Ahire

Patil

et al. 2023

Front. Cell. Infect. Microbiol.

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The chikungunya virus (CHIKV) is an alphavirus transmitted by Aedes mosquitoes. There are no licenced antivirals or vaccines for treatment or prevention. Drug repurposing approach has emerged as a novel concept to find alternative uses of therapeutics to battle pathogens. In the present study, anti CHIKV activity of fourteen FDA-approved drugs was investigated by in vitro and in silico approaches. Focus-forming unit assay, immunofluorescence test, and quantitative RT-PCR assay were used to assess the in vitro inhibitory effect of these drugs against CHIKV in Vero CCL-81 cells. The findings showed that nine compounds, viz., temsirolimus, 2-fluoroadenine, doxorubicin, felbinac, emetine, lomibuvir, enalaprilat, metyrapone and resveratrol exhibit anti chikungunya activity. Furthermore, in silico molecular docking studies performed by targeting CHIKV structural and non-structural proteins revealed that these drugs can bind to structural protein targets such as envelope protein, and capsid, and non-structural proteins NSP2, NSP3 and NSP4 (RdRp). Findings from in vitro and in silico studies reveal that these drugs can suppress the infection and replication of CHIKV and further in vivo studies followed by clinical trials are warranted.

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“…For example, several studies were conducted to investigate the impact of mutations found in both the spike protein [135,[269][270][271][272][273] and the main protease [135,198,274,275] of emerging strains on viral fitness and resistance to existing therapies. These studies showed that relatively inexpensive approaches such as homology modeling and positional scanning can be reliable tools to rationalize the origin of the virus [274,[276][277][278], quickly track the evolution of the original strain [135,279,280], predict the impact of future possible mutations [270,272] and adjust existing therapeutics tools accordingly [198,281].…”

Section: Cadd Strategies Against Covid-19mentioning

confidence: 99%

Lessons Learnt from COVID-19: Computational Strategies for Facing Present and Future Pandemics

Pavan

Moro

2023

IJMS

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Since its outbreak in December 2019, the COVID-19 pandemic has caused the death of more than 6.5 million people around the world. The high transmissibility of its causative agent, the SARS-CoV-2 virus, coupled with its potentially lethal outcome, provoked a profound global economic and social crisis. The urgency of finding suitable pharmacological tools to tame the pandemic shed light on the ever-increasing importance of computer simulations in rationalizing and speeding up the design of new drugs, further stressing the need for developing quick and reliable methods to identify novel active molecules and characterize their mechanism of action. In the present work, we aim at providing the reader with a general overview of the COVID-19 pandemic, discussing the hallmarks in its management, from the initial attempts at drug repurposing to the commercialization of Paxlovid, the first orally available COVID-19 drug. Furthermore, we analyze and discuss the role of computer-aided drug discovery (CADD) techniques, especially those that fall in the structure-based drug design (SBDD) category, in facing present and future pandemics, by showcasing several successful examples of drug discovery campaigns where commonly used methods such as docking and molecular dynamics have been employed in the rational design of effective therapeutic entities against COVID-19.

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Genomic and structural mechanistic insight to reveal the differential infectivity of omicron and other variants of concern

Cited by 7 publications

References 70 publications

Virulence Profiles of Wild-Type, P.1 and Delta SARS-CoV-2 Variants in K18-hACE2 Transgenic Mice

Virulence Profiles of Wild-Type, P.1 and Delta SARS-CoV-2 Variants in K18-hACE2 Transgenic Mice

Drug repurposing approach against chikungunya virus: an in vitro and in silico study

Lessons Learnt from COVID-19: Computational Strategies for Facing Present and Future Pandemics

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