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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Exploring the emerging trends in the synthesis and theranostic paradigms of cerium oxide nanoparticles (CeONPs): A comprehensive review

Materials Today Chemistry, Journal Year: 2024, Volume and Issue: 35, P. 101894 - 101894

Published: Jan. 1, 2024

Language: Английский

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Current perspectives and trend of computer-aided drug design: a review and bibliometric analysis

International Journal of Surgery, Journal Year: 2024, Volume and Issue: unknown

Published: March 19, 2024

Computer-aided drug design (CADD) is a technique for computing ligand-receptor interactions and involved in various stages of development. To better grasp the frontiers hotspots CADD, we conducted review analysis through bibliometrics.

Language: Английский

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Genetic Conservation and Diversity of SARS‐CoV‐2 Envelope Gene Across Variants of Concern

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(1)

Published: Jan. 1, 2025

ABSTRACT SARS‐CoV‐2 Envelope (E) protein is critical in viral assembly, release, and virulence. E gene was considered highly conserved evolving slowly. Pan‐sarbecoviruses–conserved regions the have been used as targets for various RT‐PCR assays to detect SARS‐CoV‐2. It remains elusive whether variants of concern (VOCs) accumulated significant mutations that may affect stability diagnostic assays. Herein we aimed perform a comprehensive genetic analysis on conservation diversity its VOCs comparison with other human coronaviruses (HCoVs). In silico 20 326 HCoV sequences retrieved from GenBank GISAID suggests has multiple pan‐HCoVs– pan‐SARS‐CoV‐2–conserved positions but accumulates VOC B.1.351 Omicron strains. Mutations were often found 5′ 3′ variable regions, whereas central region conserved. Nucleotide changes C109U A114G lead potential failure first‐line diagnostic/screening change C212U concomitant amino acid substitution Pro71Leu (i.e., C212U/Pro71Leu) hallmark mutation variants, while C26U/Thr9Ile characteristic all variants. Later subvariants, such XBB.1.5 EG.5, additionally acquired A31G/Thr11Ala mutation, confirmed by whole genome sequencing 118 pediatric cases. Wild‐type exhibits cytotoxicity cells, Thr9Ile, Thr11Ala, Thr9Ile + or reduces cytotoxicity. The Thr11Ala stabilizes proteins alters cellular distribution protein, reducing colocalization Golgi body. Altogether, this study not only sheds light also informs improvement development pan‐HCoVs screening

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. African trial denied access key COVID Paxlovid.Nature. 2022; 604: 412-413Crossref (9) Scholar,7Callaway E. rebound surprisingly common - even without (Preprint at)https://doi.org/10.1038/d41586-022-02121-zCrossref Scholar,8Niraj N. Mahajan Prakash Sarma P. Medhi Paxlovid: promising challenging treatment SARS-COV-2 era.Indian J. 54: 452-458PubMed Scholar,9Mohapatra R.K. Tiwari Sarangi A.K. Islam M.R. Dhama K. (B.1.1.529) SARS-CoV-2: concerns, challenges, updates.J. Med. Virol. 94: 2336-2342Crossref (59) During past years, created nature mutations S other proteins like etc.10Cappell M.S. Friedman Mikhail Chyloperitoneum associated chronic severe sarcoidosis.Am. Gastroenterol. 1993; 88: 99-101PubMed Scholar,11Chakraborty Evolution, mode transmission, mutational landscape variants.mBio. e0114021Crossref (44) These caused resistance, reported time time.12Chakraborty A detailed overview immune escape, antibody partial vaccine escape their mutations.Front. Immunol. 13: 801522Crossref (39) Scholar,13Chakraborty Emerging role small molecule-based resistance.Curr. Opin. 62: 64-73Crossref (24) Several observed subvariants that cause escape.14Chakraborty Mallik heavily mutated variant: mapped location probable properties an emphasis on S-glycoprotein.Int. Biol. Macromol. 219: 980-997Crossref (13) Scholar,15Chakraborty Continent-wide evolutionary trends variants: dynamic profiles Alpha Omicron.GeroScience. 44: 2371-2392Crossref Scholar,16Chatterjee Nag Omicron: sub-variants, pathophysiology, characteristics, immunological landscape, therapies.Viruses. 2023; 15: 167Crossref (23) Scholar,17Chakraborty rapid emergence multiple sublineages profiling via phylogenetics studies.J. Infect. Public Health. 1234-1258Crossref (10) phenomenon causes immense concern scientists. 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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Significance of Conserved Regions in Coronavirus Spike Protein for Developing a Novel Vaccine against SARS-CoV-2 Infection

Vaccines, Journal Year: 2023, Volume and Issue: 11(3), P. 545 - 545

Published: Feb. 24, 2023

Over the years, several distinct pathogenic coronaviruses have emerged, including pandemic SARS-CoV-2, which is difficult to curtail despite availability of licensed vaccines. The difficulty in managing SARS-CoV-2 linked changes variants’ proteins, especially spike protein (SP) used for viral entry. These mutations, SP, enable virus evade immune responses induced by natural infection or vaccination. However, some parts SP S1 subunit and S2 are considered conserved among coronaviruses. In this review, we will discuss epitopes proteins that been demonstrated various studies be may immunogenic development a vaccine. Considering higher conservancy S2, further likely challenges could limit from inducing robust promising approaches increase its immunogenicity.

Language: Английский

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The emergence and implications of SARS-CoV-2 omicron subvariant BA.2.86 on global health

International Journal of Surgery, Journal Year: 2024, Volume and Issue: 110(4), P. 2498 - 2501

Published: Jan. 11, 2024

The SARS-CoV-2 subvariant BA.2.86 ‘Pirola’, first identified in Denmark August 2023, has manifested with a significantly mutated spike protein profile, suggesting heightened ability to evade vaccine-induced and infection-induced antibodies. This article outlines the epidemiological spread, immune response implications, global responses BA.2.86. Preliminary observations indicate community transmissions of subvariant, even among those previously infected or vaccinated. Notably, infection shown potential amplify antibody responses. variant’s emergence evoked memories Omicron rise late 2021, though immunity levels might modulate impact differently. Continuous genomic surveillance, coupled integrated diagnostic strategies, proves crucial early detection management. reaffirms unpredictable nature COVID-19 pandemic, emphasizing need for ongoing research, adaptability, collaboration.

Language: Английский

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Mutational dynamics of SARS-CoV-2: Impact on future COVID-19 vaccine strategies

Heliyon, Journal Year: 2024, Volume and Issue: 10(9), P. e30208 - e30208

Published: April 25, 2024

The rapid emergence of multiple strains Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has sparked profound concerns regarding the ongoing evolution virus and its potential impact on global health. Classified by World Health Organization (WHO) as variants concern (VOC), these exhibit heightened transmissibility pathogenicity, posing significant challenges to existing vaccine strategies. Despite widespread vaccination efforts, continual SARS-CoV-2 presents a formidable obstacle achieving herd immunity. Of particular is coronavirus spike (S) protein, pivotal viral surface protein crucial for host cell entry infectivity. Mutations within S have been shown enhance confer resistance antibody-mediated neutralization, undermining efficacy traditional platforms. Moreover, undergoes molecular under selective immune pressure, leading diverse with distinct mutation profiles. This review underscores urgent need vigilance adaptation in development efforts combat evolving landscape mutations ensure long-term effectiveness immunization campaigns.

Language: Английский

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Peptidomimetics as potent dual SARS-CoV-2 cathepsin-L and main protease inhibitors: In silico design, synthesis and pharmacological characterization

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 266, P. 116128 - 116128

Published: Jan. 9, 2024

In this paper we present the design, synthesis, and biological evaluation of a new series peptidomimetics acting as potent anti-SARS-CoV-2 agents. Starting from our previously described Main Protease (M

Language: Английский

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Comparing the Infectivity of Recent SARS-CoV-2 Omicron Sub-Variants in Syrian Hamsters

Viruses, Journal Year: 2024, Volume and Issue: 16(1), P. 122 - 122

Published: Jan. 14, 2024

Since the emergence of first omicron SARS-CoV-2 variant at end 2021, several sub-variants have evolved and become predominant in human population, showing enhanced transmissibility ability to (partly) escape adaptive immune response. The XBB (e.g., EG.5.1) globally dominant. Besides sub-variants, a phylogenetically distinct variant, i.e., BA.2.86, is also circulating; it carries mutations spike protein as compared its parental BA.2 variant. Here, we explored infectivity BA.2.86 EG.5.1 preceding BA.5 sub-variant Syrian hamsters. Such preclinical models are important for evaluation updated vaccine candidates novel therapeutic modalities. Following intranasal infection with either throat swabs lung samples were collected on days 3 4 post infection. No significant differences viral RNA loads observed between these sub-variants. However, infectious virus titers lungs EG.5.1- BA.2.86-infected animals significantly lower BA.5-infected ones. pathology scores infected markedly than that sub-variant. Together, show exhibit an attenuated replication hamsters’

Language: Английский

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