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      Mutations in SARS-CoV-2: insights on structure, variants, vaccines, and biomedical interventions

      review-article
      Author(s): a , b , c , d , 1 , * , a , e , a , a , a , a , b , f , g , h , ** , i , i , j , k , l , m , m , n , o , 2 , **
      Publication date (Electronic):
      Journal: Biomedicine & Pharmacotherapy
      Publisher: The Author(s). Published by Elsevier Masson SAS.
      Keywords: ACE2, angiotensin-converting enzyme 2, BIBP, Beijing Institute of biological products, CD, cluster of differentiation, CDC, Centers for Disease Control and Prevention, COVID-19, coronavirus disease 2019, CRP, C-reactive protein, CTD, C-terminal domains, E, envelope, ELISA, enzyme-linked immunosorbent assay, ERGIC, endoplasmic reticulum–Golgi intermediate compartment, ESR, erythrocyte sedimentation rate, FP, fusion-peptide, GCSF, granulocyte colony-stimulating factor, GISAID, Global Initiative on Sharing Avian Influenza Data, GMTs, geometric mean titers, HCoVs, human coronaviruses, ICU, intensive care unit, Ig, immunoglobulin, IL, interleukin, LDH, lactate dehydrogenase, LNPs, lipid nanoparticles, M, membrane, MERS-CoV, Middle East respiratory syndrome coronavirus, mRNA, messenger RNA, N, nucleocapsid, NABs, neutralization antibodies, Nsp, non-structural proteins, NTD, N-terminal domain, nts, nucleotides, ORFs, open reading frames, PANGOLIN, phylogenetic assignment of named global outbreak lineages, PCR, polymerase chain reaction, pp, polyproteins, r, recombinant, RBD, receptor-binding domain, RdRP, RNA dependent RNA polymerase, RDT, rapid diagnostic test, RNA, ribonucleic acid, ROCM, rhino-orbital-cerebral mucormycosis, S, spike, SARS-CoV, severe acute respiratory syndrome coronavirus, sgRNA, subgenomic RNA, SNP, single nucleotide polymorphism, TAG-VE, Technical Advisory Organization on SARS-CoV-2 Virus Evolution, TMPRSS2, transmembrane protease serine-2, TNF, tumor necrosis factor, VOC, variant of concern, VOHC, variants of high consequences, VOI, variant of interest, WHO, World Health Organization, αCoV, Alpha coronavirus, βCoV, Beta coronavirus, γCoV, Gamma coronavirus, δCoV, Delta coronavirus, SARS-CoV-2, Mutation, Variants, Pandemic disease, Vaccines

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          Abstract

          COVID-19 is a worldwide pandemic caused by SARS-coronavirus-2 (SARS-CoV-2). Less than a year after the emergence of the Covid-19 pandemic, many vaccines have arrived on the market with innovative technologies in the field of vaccinology. Based on the use of messenger RNA (mRNA) encoding the Spike SARS-Cov-2 protein or on the use of recombinant adenovirus vectors enabling the gene encoding the Spike protein to be introduced into our cells, these strategies make it possible to envisage the vaccination in a new light with tools that are more scalable than the vaccine strategies used so far. Faced with the appearance of new variants, which will gradually take precedence over the strain at the origin of the pandemic, these new strategies will allow a much faster update of vaccines to fight against these new variants, some of which may escape neutralization by vaccine antibodies. However, only a vaccination policy based on rapid and massive vaccination of the population but requiring a supply of sufficient doses could make it possible to combat the emergence of these variants. Indeed, the greater the number of infected individuals, the faster the virus multiplies, with an increased risk of the emergence of variants in these RNA viruses. This review will discuss SARS-CoV-2 pathophysiology and evolution approaches in altered transmission platforms and emphasize the different mutations and how they influence the virus characteristics. Also, this article summarizes the common vaccines and the implication of the mutations and genetic variety of SARS-CoV-2 on the COVID-19 biomedical arbitrations.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

            Fei Zhou, Ting Yu, Ronghui Du … (2020)
            Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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              Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

              Dawei Wang, Bo Hu, Fangfang Zhu … (2020)
              In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
              Article 0 comments Cited 10920 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Biomed Pharmacother
                Journal ID (iso-abbrev): Biomed Pharmacother
                Title: Biomedicine & Pharmacotherapy
                Publisher: The Author(s). Published by Elsevier Masson SAS.
                ISSN (Print): 0753-3322
                ISSN (Electronic): 1950-6007
                Publication date PMC-release: 7 November 2022
                Publication date (Electronic): 7 November 2022
                Electronic Location Identifier: 113977
                Affiliations
                [a ]Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
                [b ]Department of Biochemistry and Biotechnology, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
                [c ]Laboratory of Veterinary Surgery, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi, Tokyo 183-8509, Japan
                [d ]Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh, Elqaliobiya,13736, Egypt
                [e ]Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City 11829, Cairo, Egypt
                [f ]Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi, Tokyo 183-8509, Japan
                [g ]Department of Animal Hygiene, Behavior and Management, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh, Elqaliobiya 13736, Egypt
                [h ]Department of Vegetable Crops and Medicinal Plants University of Life Sciences in Lublin 50A Doświadczalna Street, 20-280 Lublin, Poland
                [i ]Department of Laboratory & Blood Bank, Security Forces Hospital, P.O. Box 14799, Mecca, 21955, Saudi Arabia
                [j ]College of Medicine, Al-Faisal University, P.O. Box 50927, Riyadh, 11533, Saudi Arabia
                [k ]Department of Clinical Laboratory sciences, College of Applied medical sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
                [l ]Department of Human Anatomy, College of Medicine, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia
                [m ]Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231 Jeddah 21442, Saudi Arabia
                [n ]Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt
                [o ]Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt
                Author notes
                [* ]Corresponding author at. Laboratory of Veterinary Surgery, Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi, Tokyo 183-8509, Japan. Fax: +81-42-367-5904
                [** ]Corresponding authors.
                [1]

                ORCID: https://orcid.org/0000-0003-1143-4018

                [2]

                ORCID: https://orcid.org/0000-0002-0136-7096

                Article
                Publisher Item ID: S0753-3322(22)01366-X Publisher ID: 113977
                DOI: 10.1016/j.biopha.2022.113977
                PMC ID: 9637516
                PubMed ID: 36370519
                SO-VID: da054289-787a-4bac-a228-e8677363536e
                Copyright © © 2022 The Authors
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 13 October 2022
                Date revision received : 29 October 2022
                Date accepted : 3 November 2022
                Categories
                Subject: Article

                Keywords: ace2, angiotensin-converting enzyme 2,bibp, beijing institute of biological products,cd, cluster of differentiation,cdc, centers for disease control and prevention,covid-19, coronavirus disease 2019,crp, c-reactive protein,ctd, c-terminal domains,e, envelope,elisa, enzyme-linked immunosorbent assay,ergic, endoplasmic reticulum–golgi intermediate compartment,esr, erythrocyte sedimentation rate,fp, fusion-peptide,gcsf, granulocyte colony-stimulating factor,gisaid, global initiative on sharing avian influenza data,gmts, geometric mean titers,hcovs, human coronaviruses,icu, intensive care unit,ig, immunoglobulin,il, interleukin,ldh, lactate dehydrogenase,lnps, lipid nanoparticles,m, membrane,mers-cov, middle east respiratory syndrome coronavirus,mrna, messenger rna,n, nucleocapsid,nabs, neutralization antibodies,nsp, non-structural proteins,ntd, n-terminal domain,nts, nucleotides,orfs, open reading frames,pangolin, phylogenetic assignment of named global outbreak lineages,pcr, polymerase chain reaction,pp, polyproteins,r, recombinant,rbd, receptor-binding domain,rdrp, rna dependent rna polymerase,rdt, rapid diagnostic test,rna, ribonucleic acid,rocm, rhino-orbital-cerebral mucormycosis,s, spike,sars-cov, severe acute respiratory syndrome coronavirus,sgrna, subgenomic rna,snp, single nucleotide polymorphism,tag-ve, technical advisory organization on sars-cov-2 virus evolution,tmprss2, transmembrane protease serine-2,tnf, tumor necrosis factor,voc, variant of concern,vohc, variants of high consequences,voi, variant of interest,who, world health organization,αcov, alpha coronavirus,βcov, beta coronavirus,γcov, gamma coronavirus,δcov, delta coronavirus,sars-cov-2,mutation,variants,pandemic disease,vaccines
                Data availability:
                Keywords: ace2, angiotensin-converting enzyme 2, bibp, beijing institute of biological products, cd, cluster of differentiation, cdc, centers for disease control and prevention, covid-19, coronavirus disease 2019, crp, c-reactive protein, ctd, c-terminal domains, e, envelope, elisa, enzyme-linked immunosorbent assay, ergic, endoplasmic reticulum–golgi intermediate compartment, esr, erythrocyte sedimentation rate, fp, fusion-peptide, gcsf, granulocyte colony-stimulating factor, gisaid, global initiative on sharing avian influenza data, gmts, geometric mean titers, hcovs, human coronaviruses, icu, intensive care unit, ig, immunoglobulin, il, interleukin, ldh, lactate dehydrogenase, lnps, lipid nanoparticles, m, membrane, mers-cov, middle east respiratory syndrome coronavirus, mrna, messenger rna, n, nucleocapsid, nabs, neutralization antibodies, nsp, non-structural proteins, ntd, n-terminal domain, nts, nucleotides, orfs, open reading frames, pangolin, phylogenetic assignment of named global outbreak lineages, pcr, polymerase chain reaction, pp, polyproteins, r, recombinant, rbd, receptor-binding domain, rdrp, rna dependent rna polymerase, rdt, rapid diagnostic test, rna, ribonucleic acid, rocm, rhino-orbital-cerebral mucormycosis, s, spike, sars-cov, severe acute respiratory syndrome coronavirus, sgrna, subgenomic rna, snp, single nucleotide polymorphism, tag-ve, technical advisory organization on sars-cov-2 virus evolution, tmprss2, transmembrane protease serine-2, tnf, tumor necrosis factor, voc, variant of concern, vohc, variants of high consequences, voi, variant of interest, who, world health organization, αcov, alpha coronavirus, βcov, beta coronavirus, γcov, gamma coronavirus, δcov, delta coronavirus, sars-cov-2, mutation, variants, pandemic disease, vaccines

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