A Detailed Overview of SARS-CoV-2 Omicron: Its Sub-Variants, Mutations and Pathophysiology, Clinical Characteristics, Immunological Landscape, Immune Escape, and Therapies

Viruses, Journal Year: 2023, Volume and Issue: 15(1), P. 167 - 167

Published: Jan. 5, 2023

The COVID-19 pandemic has created significant concern for everyone. Recent data from many worldwide reports suggest that most infections are caused by the Omicron variant and its sub-lineages, dominating all previously emerged variants. numerous mutations in Omicron’s viral genome sub-lineages attribute it a larger amount of fitness, owing to alteration transmission pathophysiology virus. With rapid change structure, sub-variants, namely BA.1, BA.2, BA.3, BA.4, BA.5, dominate community with an ability escape neutralization efficiency induced prior vaccination or infections. Similarly, several recombinant sub-variants Omicron, XBB, XBD, XBF, etc., have emerged, which better understanding. This review mainly entails changes due having higher number mutations. binding affinity, cellular entry, disease severity, infection rates, importantly, immune evading potential them discussed this review. A comparative analysis Delta other variants evolved before gives readers in-depth understanding landscape infection. Furthermore, discusses range abilities possessed approved antiviral therapeutic molecules neutralizing antibodies functional against sub-variants. evolution is causing infections, but broader aspect their not been explored. Thus, scientific should adopt elucidative approach obtain clear idea about recently including variants, so effective vaccines drugs can be achieved. This, turn, will lead drop cases and, finally, end pandemic.

Language: Английский

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SARS-CoV-2 Vaccines, Vaccine Development Technologies, and Significant Efforts in Vaccine Development during the Pandemic: The Lessons Learned Might Help to Fight against the Next Pandemic

Vaccines, Journal Year: 2023, Volume and Issue: 11(3), P. 682 - 682

Published: March 17, 2023

We are currently approaching three years since the beginning of coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 has caused extensive disruptions in everyday life, public health, and global economy. Thus far, vaccine worked better than expected against virus. During pandemic, we experienced several things, such as virus its pathogenesis, clinical manifestations, treatments; emerging variants; different vaccines; development processes. This review describes how each been developed approved with help modern technology. also discuss critical milestones during process. Several lessons were learned from countries two research, development, trials, vaccination. The process will to fight next

Language: Английский

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Global landscape of SARS-CoV-2 mutations and conserved regions

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Feb. 25, 2023

Abstract Background At the end of December 2019, a novel strain Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) disease (COVID-19) has been identified in Wuhan, central city China, and then spread to every corner globe. As October 8, 2022, total number COVID-19 cases had reached over 621 million worldwide, with more than 6.56 confirmed deaths. Since SARS-CoV-2 genome sequences change due mutation recombination, it is pivotal surveil emerging variants monitor changes for improving pandemic management. Methods 10,287,271 sequence samples were downloaded FASTA format from GISAID databases February 24, 2020, April 2022. Python programming language (version 3.8.0) software was utilized process files identify conservation. The NCBI RefSeq (accession no. NC_045512.2) considered as reference sequence. Results Six mutations 50% frequency global SARS-CoV-2. These include P323L (99.3%) NSP12, D614G (97.6) S, T492I (70.4) NSP4, R203M (62.8%) N, T60A (61.4%) Orf9b, P1228L (50.0%) NSP3. In genome, no observed 90% nsp11, nsp7, nsp10, nsp9, nsp8, nsp16 regions. On other hand, nsp3, nsp4, nsp12, M maximum rate mutations. S protein, highest aa 508–635(0.77%) 381–508 (0.43%). 66–88 (2.19%), 7–14, 164–246 (2.92%) M, E, N proteins, respectively. Conclusion Therefore, monitoring proteomic detecting hot spots conserved regions could be applied improve SARS‐CoV‐2 diagnostic efficiency design safe effective vaccines against variants.

Language: Английский

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Resistance to nirmatrelvir due to mutations in the Mpro in the subvariants of SARS-CoV-2 Omicron: Another concern?

Molecular Therapy — Nucleic Acids, Journal Year: 2023, Volume and Issue: 32, P. 263 - 266

Published: April 6, 2023

The world has faced 3 years of the COVID-19 pandemic with billions infections, millions deaths, and a massive economic crisis. Since began, scientists have started to fight against SARS-CoV-2. One significant scientific effort was searching for successful therapeutic molecules virus. repurposing drug candidates initiated in initial stage pandemic.1Cantini F. Goletti D. Petrone L. Najafi Fard S. Niccoli Foti R. Immune therapy, or antiviral both COVID-19: systematic review.Drugs. 2020; 80: 1929-1946Crossref PubMed Scopus (71) Google Scholar,2Chakraborty C. Sharma A.R. Bhattacharya M. Agoramoorthy G. Lee S.S. clinical trials provide very effective combinations: lessons learned from major studies.Front. Pharmacol. 2021; 12: 704205Crossref (56) Scholar,3Saha R.P. Singh M.K. Samanta Bhakta Mandal Chakraborty Repurposing drugs, ongoing vaccine, new development initiatives COVID-19.Front. 11: 1258Crossref (84) Scholar Along repurposing, molecule discovery by exploring targets. most targets are RdRp, Mpro/3CLpro, others.4More S.A. Patil A.S. Sakle N.S. Mokale S.N. Network analysis molecular mapping SARS-CoV-2 reveal clinically developed drugs.Virology. 555: 10-18Crossref (15) Scholar,5Chakraborty Mallick B. protein landscape: potential pharmacological insight view development.Expet Rev. Clin. 14: 225-238Crossref possible repurposed newly discovered been tested vivo, vitro, through trials. They found several this virus, such as nirmatrelvir, ritonavir, remdesivir, molnupiravir, etc. recent Omicron variant its subvariant is Paxlovid, which combines two (nirmatrelvir ritonavir). Paxlovid shows high effectiveness emerging variants subvariants.6Ledford H. Maxmen A. 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Recently, noted might be responsible nirmatrelvir resistance (Figure 1). acquired wide range non-structural during generation. allowed it adjust quickly environment, increase infectivity rate, eventually develop due hotspot residues. This actually survival. FDA approved (an component Paxlovid) treating mild-to-moderate infections combat developing variations predominantly subvariants.18Padhi Tripathi T. Hotspot residues nirmatrelvir-binding site main protease: design, identification, correlation globally circulating viral genomes.Biochem. Biophys. Res. Commun. 629: 54-60Crossref (12) It proven oral 3CL protease SARS-CoV-2, pandemic.19Iketani Mohri Culbertson Hong S.J. Duan Y. Luck M.I. Annavajhala Guo Sheng Z. Uhlemann A.C. et al.Multiple pathways nirmatrelvir.Nature. 613: 558-564Crossref (63) interacts Cys145 residue nsp5 establishing covalent bond.20Lan Neilsen Slack R.L. Cantara W.A. Castaner A.E. Lorson Z.C. Lulkin N.D. Zhang Cilento M.E. Tedbury P.R. Nirmatrelvir Omicron_BA.1 WA1 replicons strategies.bioRxiv. at)https://doi.org/10.1101/2022.12.31.522389Crossref (0) New potently evade currently available therapeutics continue arise intense selective pressure spike glycoprotein. Many so far.21Willett B.J. Grove MacLean O.A. Wilkie De Lorenzo Furnon W. Cantoni Scott Logan Ashraf al.SARS-CoV-2 altered cell entry pathway.Nat. Microbiol. 7: 1161-1179Crossref (161) Scholar,22Greaney A.J. Starr T.N. Gilchuk Zost Binshtein Loes A.N. Hilton S.K. Huddleston Eguia Crawford K.H.D. al.Complete receptor-binding domain recognition.Cell Host Microbe. 29: 44-57.e9Abstract Full Text PDF (564) Scholar,23Greaney Malone K.D. Chu H.Y. Bloom J.D. Comprehensive affect recognition polyclonal human plasma antibodies.Cell 463-476.e6Abstract (618) Scholar,24Kudriavtsev A.V. Vakhrusheva Novoseletsky C.V.N. Bozdaganyan Shaitan K.V. Kirpichnikov M.P. Sokolova O.S. RBD evolution dynamics.Viruses. 1603Crossref (11) Antiviral treatments crucial those who not immunized cases illness suddenly. Because vital coronavirus replication, coronaviruses makes extremely target.21Willett SARS 2002 more pandemic, (Mpro/3CLpro) (CoV) family initially investigated target designing various therapeutics.25Anand Ziebuhr Wadhwani Mesters J.R. Hilgenfeld Coronavirus proteinase (3CLpro) structure: basis design anti-SARS drugs.Science. 2003; 300: 1763-1767Crossref (1359) Scholar,26Boras Jones R.M. Anson Arenson Aschenbrenner Bakowski M.A. Beutler Binder Chen Eng al.Preclinical characterization intravenous inhibitor COVID19.Nat. 6055Crossref (130) Scholar,27Service R.F. call arms.Science. 371: 1092-1095Crossref (7) results obtained constructing inhibitors hepatitis C virus (HCV) HIV-1 instigated similar treat infection.28Flexner HIV-protease inhibitors.N. Engl. 1998; 338: 1281-1292Crossref (772) Scholar,29Anderson Schiffer Swanstrom Viral inhibitors.Handb. Exp. 2009; 189: 85-110Crossref (94) viruses now circulation Mpro make them resistant nirmatrelvir. For instance, M49I mutation 1,883 genomes May 2022, minor late 2021.30Sedova Jaroszewski Iyer Godzik Monitoring broad populations.bioRxiv. at)https://doi.org/10.1101/2022.05.27.493798Crossref Sasi al. highlighted potency decreased five mutations, namely Q189E, Q192T, N142L, Q189I, E166M. IC50 reduced factor 24 E166M mutation.31Sasi V.M. Ullrich Ton Fry S.E. Johansen-Leete Payne R.J. Nitsche Jackson C.J. Predicting computational experimental screening.Biochemistry. 61: 2495-2505Crossref According phylogenetic analyses, nirmatrelvir-resistant transmissible appear existed before introduced into population.32Moghadasi Heilmann Moraes Kearns F.L. von Laer Amaro R.E. al.Transmissible inhibitors.bioRxiv. at)https://doi.org/10.1101/2022.08.07.503099Crossref In addition, Lan al.20Lan designed specific hinder nirmatrelvir’s ability attach substrate study resistance. used 12 wild-type one (BA.1), followed enzymatic assays cell-based complementation. result demonstrated E166V conferred strong approximately 55-fold, drop replicon fitness (nearly 20-fold), but BA.1 (2-fold), cases. However, L50F improved replicons. Due these variations, possibly may lower barrier than variant.20Lan Despite prevalent variant, P132H, maintained vitro efficacy Omicron, BQ.1.1,33Imai Ito Kiso Yamayoshi Uraki Fukushi Watanabe Suzuki Maeda Sakai-Tagawa al.Efficacy agents BQ.1.1 XBB.N. 388: 89-91Crossref (77) XBB,33Imai BA.1,34Greasley Noell Plotnikova O. Ferre Liu Bolanos Fennell Nicki Craig Zhu al.Structural variants.J. Chem. 298: 101972Abstract BA.1.1,35Takashita Simon V. van Bakel Sordillo E.M. Pekosz Halfmann antibodies drugs BA.2.12.1, BA.4, BA.5 subvariants.N. 387: 468-470Crossref (132) BA.5,35Takashita BA.4,35Takashita BA.2,35Takashita BA.2.12.1,35Takashita BA.2.75.36Saito Tamura Zahradnik Deguchi Tabata Anraku Kimura I. Yamasoba Nasser al.Virological characteristics BA.2.75 variant.Cell 30: 1540-1555.e15Abstract (37) outcomes testing encouraging, there still many challenges widespread application. First, participants received when infection early stages. practice, can administer antivirals patients soon they diagnosed positive. Second, despite careful patient selection, monotherapy produces suboptimal results.37Mahase Covid-19: pfizer's paxlovid 89% at risk serious illness, company reports.BMJ. 375: n2713Crossref (249) Scholar,38Jayk Bernal Gomes da Silva M.M. Musungaie D.B. Kovalchuk Gonzalez Delos Reyes Martín-Quirós Caraco Williams-Diaz Brown M.L. al.Molnupiravir covid-19 Nonhospitalized patients.N. 386: 509-520Crossref (839) shown reduce hamsters’ respiratory organs after infected BA.2 variant.39Uraki Iida Imai Takashita Kuroda P.J. Loeber Maemura al.Characterization susceptibility BA.2.Nature. 607: 119-127Crossref (112) transmission suppressed entirely group animals given human-equivalent dose molnupiravir. Still, pharmacokinetic did significantly titers ferrets. also prevent untreated ferrets direct contact. While prophylactic resulted all contacts, molnupiravir uninfected close prevented transmission.40Cox Lieber C.M. Wolf Karimi Lieberman N.A.P. Sticher Z.M. Roychoudhury Andrews Krueger Natchus M.G. al.Paxlovid-like nirmatrelvir/ritonavir fails block ferrets.bioRxiv. An Iketani al.19Iketani 13 recombinant clones revealed higher levels needed accumulation further because three noteworthy T21I, P252L, T304I, only low-level 100-fold). replicate, later recovered compensatory modifications T21I L50F. show variety pathways, unique here solid framework investigate mechanism detail guide potent future generations.19Iketani dynamics simulations, combination E166M, alone, binding between Mpro. polymerase remdesivir bebtelovimab (a monoclonal antibody) anti-nirmatrelvir activity lineages. compounds compared administration individual components. discoveries how therapies monitored ensured effective.41Zhou Gammeltoft K.A. Ryberg L.A. Pham L.V. Tjørnelund H.D. Binderup Duarte Hernandez C.R. Fernandez-Antunez Offersgaard Fahnøe U. al.Nirmatrelvir-resistant infectious culture system.Sci. Adv. 8: eadd7197Crossref (35) quick aggressive preclinical helped health care burden 2022. exceptionally efficient combating wave, preserved efficacy. first quarter generated $1.5 billion sales, making prescribed throughout world.42Gold J.A.W. Kelleher Magid B.R. Pennini Kushner Weston E.J. Rasulnia Kuwabara Bennett al.Dispensing zip code-level social vulnerability United States, december 23, 2021-may 21, 2022.MMWR Morb. Mortal. Wkly. Rep. 71: 825-829Crossref When taken, system actively destroys including any potentially versions developed. sense concentrate efforts surveillance immunocompromised receiving detect drug-resistant If medication could chosen happened previously will undoubtedly produce vivo. Although existing monotherapies, feasible beneficial employing cocktail possibility escape.19Iketani Therefore, need work cocktails discover options Simultaneously, would help pandemic. authors confirm data supporting findings within article.

Language: Английский

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The Anti-SARS-CoV-2 IgG1 and IgG3 Antibody Isotypes with Limited Neutralizing Capacity against Omicron Elicited in a Latin Population a Switch toward IgG4 after Multiple Doses with the mRNA Pfizer–BioNTech Vaccine

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 187 - 187

Published: Jan. 26, 2024

The aim of this study was to analyze the profiles IgG subclasses in COVID-19 convalescent Puerto Rican subjects and compare these with those non-infected immunocompetent or immunocompromised that received two more doses an mRNA vaccine. most notable findings from are as follows: (1) Convalescent were not hospitalized developed high long-lasting antibody responses. (2) Both IgG1 IgG3 prevalent SARS-CoV-2-infected population, whereas after vaccination. (3) Individuals infected then later vaccine exhibited a robust neutralizing capacity against Omicron than never (4) A class switch toward "anti-inflammatory" isotype IgG4 induced few weeks third dose, which peaked abruptly remained at levels for long period. Moreover, concurrent percentages various VOCs including Omicron. (5) Subjects IBD also produced antibodies although had limited effect on capacity. Knowing vaccines do prevent infections, subvariants have been shown be less pathogenic, associated immunotolerance numerous negative effects, recommendations successive administration booster vaccinations people should revised.

Language: Английский

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The rapid emergence of multiple sublineages of Omicron (B.1.1.529) variant: Dynamic profiling via molecular phylogenetics and mutational landscape studies

Journal of Infection and Public Health, Journal Year: 2022, Volume and Issue: 15(11), P. 1234 - 1258

Published: Oct. 13, 2022

The recent Omicron (B.1.1.529) variant poses a significant threat to global health. This has spread worldwide, and several sublineages have rapidly emerged. Study tried analyze the microevolution of this variant.

Language: Английский

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Exploring the structural and molecular interaction landscape of nirmatrelvir and Mpro complex: The study might assist in designing more potent antivirals targeting SARS-CoV-2 and other viruses

Journal of Infection and Public Health, Journal Year: 2023, Volume and Issue: 16(12), P. 1961 - 1970

Published: Sept. 30, 2023

Several therapeutics have been developed and approved against SARS-CoV-2 occasionally; nirmatrelvir is one of them. The drug target Mpro, therefore, it necessary to comprehend the structural molecular interaction Mpro-nirmatrelvir complex.Integrative bioinformatics, system biology, statistical models were used analyze macromolecular complex.Using two complexes, study illustrated interactive residues, H-bonds, interfaces. It informed six nine H-bond formations for first second complex, respectively. maximum bond length was observed as 3.33 Å. ligand binding pocket's surface area volume noted 303.485 Å2 295.456 Å3 complex 308.397 304.865 complex. proteome dynamics evaluated by analyzing complex's NMA mobility, eigenvalues, deformability, B-factor. Conversely, a model created assess therapeutic status nirmatrelvir.Our reveals landscape will guide researchers in designing more broad-spectrum antiviral molecules mimicking nirmatrelvir, which assist fighting other infectious viruses. also help prepare future epidemics or pandemics.

Language: Английский

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The Anti-SARS-CoV-2 IgG1 and IgG3 Antibody Isotypes with Limited Neutralizing Capacity against Omicron Elicited in a Latin Population Switch toward IgG4 after Multiple Doses with the mRNA Pfizer-BioNTech Vaccine.

Published: Jan. 10, 2024

The aim of this study was to analyze the profile IgG subclasses in COVID-19 convalescent Puerto Rican subjects and compare with those exhibited by no-infected immunocompetent or immunocompromised that received mRNA vaccine. most notable find-ngs from are: 1) Convalescent were not hospitalized developed high long-lasting antibody response. 2) Both, IgG1 IgG3 are more prevalent SARS-CoV-2 infected population whereas is after vaccination. 3) Individuals first had infection further two doses vaccines robust neutralizing capacity against Omicron than never Pfizer-BioNTech 4) A class switch toward “anti-inflammatory” anti-body isotype IgG4 induced a few weeks third dose, which peaked abruptly remained at levels for long period. Moreover, concurrent percentages various VOC including Omicron. 5) Subjects IBD also develop although these have limited effect on capacity. Knowing do prevent reinfections, all sub-variants dominant worldwide shown be less pathogenic, been associated immunotolerance causative numerous negative effects, recommendations successive administration booster vaccinations people should revised.

Language: Английский

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PRIEST: predicting viral mutations with immune escape capability of SARS-CoV-2 using temporal evolutionary information

Briefings in Bioinformatics, Journal Year: 2024, Volume and Issue: 25(3)

Published: March 27, 2024

Abstract The dynamic evolution of the severe acute respiratory syndrome coronavirus 2 virus is primarily driven by mutations in its genetic sequence, culminating emergence variants with increased capability to evade host immune responses. Accurate prediction such fundamental mitigating pandemic spread and developing effective control measures. This study introduces a robust interpretable deep-learning approach called PRIEST. innovative model leverages time-series viral sequences foresee potential mutations. Our comprehensive experimental evaluations underscore PRIEST’s proficiency accurately predicting immune-evading work represents substantial step utilizing methodologies for anticipatory mutation analysis response.

Language: Английский

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Impact of vaccination on SARS-CoV-2 evolution and immune escape variants

Vaccine, Journal Year: 2024, Volume and Issue: 42(21), P. 126153 - 126153

Published: Aug. 1, 2024

Language: Английский

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