Interactions of the Receptor Binding Domain of SARS-CoV-2 Variants with hACE2: Insights from Molecular Docking Analysis and Molecular Dynamic Simulation

Biology, Journal Year: 2021, Volume and Issue: 10(9), P. 880 - 880

Published: Sept. 7, 2021

Since the beginning of coronavirus 19 (COVID-19) pandemic in late 2019, severe acute respiratory syndrome 2 (SARS-CoV-2) has been evolving through acquisition genomic mutations, leading to emergence multiple variants concern (VOCs) and interest (VOIs). Currently, four VOCs (Alpha, Beta, Delta, Gamma) seven VOIs (Epsilon, Zeta, Eta, Theta, Iota, Kappa, Lambda) SARS-CoV-2 have identified worldwide circulation. Here, we investigated interactions receptor-binding domain (RBD) five with human angiotensin-converting enzyme (hACE2) receptor host cells, determine extent molecular divergence impact mutation, using protein-protein docking dynamics simulation approaches. Along wild-type (WT) SARS-CoV-2, this study included Brazilian (BR/lineage P.1/Gamma), Indian (IN/lineage B.1.617/Delta), South African (SA/lineage B.1.351/Beta), United Kingdom (UK/lineage B.1.1.7/Alpha), States (US/lineage B.1.429/Epsilon) variants. The studies revealed that these point mutations considerably affected structural behavior spike (S) protein compared WT, which also binding RBD hACE2 at respective sites. Additional experimental are required whether effects an influence on drug-S its potential therapeutic effect.

Language: Английский

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ORF3a Protein of Severe Acute Respiratory Syndrome Coronavirus 2 Inhibits Interferon-Activated Janus Kinase/Signal Transducer and Activator of Transcription Signaling via Elevating Suppressor of Cytokine Signaling 1

Frontiers in Microbiology, Journal Year: 2021, Volume and Issue: 12

Published: Sept. 28, 2021

Coronavirus disease 2019 (COVID-19) has caused a crisis to global public health since its outbreak at the end of 2019. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pathogen COVID-19, appears efficiently evade host immune responses, including interferon (IFN) signaling. Several SARS-CoV-2 viral proteins are believed involve in inhibition IFN In this study, we discovered that ORF3a, an accessory protein SARS-CoV-2, inhibited IFN-activated Janus kinase (JAK)/signal transducer and activator transcription (STAT) signaling via upregulating suppressor cytokine 1 (SOCS1), negative regulator ORF3a induced SOCS1 elevation dose- time-dependent manner. RNAi-mediated silencing abolished ORF3a-induced blockage JAK/STAT Interestingly, found also promoted ubiquitin-proteasomal degradation (JAK2), important Silencing by siRNA distinctly blocked JAK2 ubiquitination degradation. These results demonstrate dampens SOCS1, which suppressed STAT1 phosphorylation accelerated Furthermore, analysis deletion constructs showed middle domain (amino acids 70–130) was responsible for upregulation. findings contribute our understanding mechanism antagonizing antiviral response.

Language: Английский

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Severity, Pathogenicity and Transmissibility of Delta and Lambda Variants of SARS-CoV-2, Toxicity of Spike Protein and Possibilities for Future Prevention of COVID-19

Microorganisms, Journal Year: 2021, Volume and Issue: 9(10), P. 2167 - 2167

Published: Oct. 18, 2021

The World Health Organization reports that SARS-CoV-2 has infected over 220 million people and claimed 4.7 lives globally. While there are new effective vaccines, the differences in behavior of variants causing challenges vaccine development or treatment. Here, we discuss Delta, a variant concern, Lambda, interest. They demonstrate high infectivity less responsive to immune response vaccinated individuals. In this review, briefly summarize reason for severity novel variants. Delta Lambda exhibit more changes NSPs proteins S protein, compared original Wuhan strain. also numerous amino acid substitutions proteins, plus deletion NTD leading partial escape from neutralizing antibodies (NAbs) We role furin protease ACE2 receptor virus infection, hotspot mutations toxicity protein increased pathogenicity future therapeutic strategies, including those based on stability epitopes, conservation N intracellular antibody receptor, tripartite-motif 21 (TRIM21) recognized by against protein.

Language: Английский

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Basic virology of SARS-CoV 2

Indian Journal of Medical Microbiology, Journal Year: 2022, Volume and Issue: 40(2), P. 182 - 186

Published: March 14, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly transmissible pathogenic emerged in late 2019 causing pandemic of disease, named 'coronavirus disease 2019' (COVID-19). It has spread fast all over the world posing an extraordinary threat to global public health. Along with SARS-CoV-2, there are seven human coronaviruses. Those mild diseases 229E, OC43, NL63 and HKU1, ones SARSCoV, MERS-CoV SARS-CoV-2. This review highlighted basic virology SARS CoV-2 including its origin, structure, genomic characteristics, pathogenesis, immunological response clinical manifestation along key difference CoV2 from previous Coronaviruses. Coronaviruses spherical enveloped club-shaped spikes on surface. large positive sense, single stranded RNA genome within nucleocapsid helical symmetry. been known cause infection innumerable mammalian hosts, like humans, cats, bats, civets, dogs, camels. The viral contains four major structural proteins: spike (S), membrane (M), envelope (E) (N) protein encoded 3' end genome. Virus binds host cell by S specific receptor. Following receptor binding, virus enters cytosol fusion cellular membranes followed translation RNA. replication sub-genomic synthesis, formation mature virus. virions then transported surface vesicles released exocytosis.

Language: Английский

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A Review of SARS-CoV-2 Disease (COVID-19): Pandemic in Our Time

Pathogens, Journal Year: 2022, Volume and Issue: 11(3), P. 368 - 368

Published: March 17, 2022

Development and deployment of biosensors for the rapid detection 2019 novel severe acute respiratory syndrome—coronavirus 2 (SARS-CoV-2) are utmost importance urgency during this recent outbreak coronavirus pneumonia (COVID-19) caused by SARS-CoV-2 infection, which spread rapidly around world. Cases now confirmed in February 2022 indicate that more than 170 countries worldwide affected. Recent evidence indicates over 430 million cases with 5.92 deaths scattered across globe, United States having 78 920,000 deaths. The US has many China where were first reported late December 2019. During initial China, leaders did not anticipate it could reach whole world, spreading to posing threats global health. objective review is summarize origin COVID-19, its biological nature, comparison other coronaviruses, symptoms, prevention, treatment, potential, available methods detection, post-COVID-19 symptoms.

Language: Английский

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