SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(3), С. 1716 - 1716

Опубликована: Фев. 2, 2022

The review aims to consolidate research findings on the molecular mechanisms and virulence pathogenicity characteristics of coronavirus disease (COVID-19) causative agent, severe acute respiratory syndrome 2 (SARS-CoV-2), their relevance four typical stages in development viral infection. These are invasion; primary blockade antiviral innate immunity; engagement virus’s protection against factors adaptive acute, long-term complications COVID-19. invasion stage entails recognition spike protein (S) SARS-CoV-2 target cell receptors, namely, main receptor (angiotensin-converting enzyme 2, ACE2), its coreceptors, potential alternative receptors. presence a diverse repertoire receptors allows infect various types cells, including those not expressing ACE2. During second stage, majority polyfunctional structural, non-structural, extra proteins synthesizes infected cells involved blockage immunity. A high degree redundancy systemic action characterizing these pathogenic overcome at initial invasion. third includes passive active virus from immunity, overcoming barrier function focus inflammation, generalization body. fourth is associated with deployment variants SARS-CoV-2’s ability induce autoimmune autoinflammatory pathways tissue both immunosuppressive hyperergic inflammation critical this

Язык: Английский

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Mutations and Evolution of the SARS-CoV-2 Spike Protein

Viruses, Год журнала: 2022, Номер 14(3), С. 640 - 640

Опубликована: Март 19, 2022

The SARS-CoV-2 spike protein mediates target recognition, cellular entry, and ultimately the viral infection that leads to various levels of COVID-19 severities. Positive evolutionary selection mutations within has led genesis new variants with greatly enhanced overall fitness. Given trend increased fitness arising from alterations, it is critical scientific community understand mechanisms by which these alter functions. As March 2022, five strains were labeled “variants concern” World Health Organization: Alpha, Beta, Gamma, Delta, Omicron variants. This review summarizes potential common on occur enhance their respective In addressing context structure, spike/receptor binding interface, spike/antibody binding, virus neutralization, we summarize general paradigms can be used estimate effects future along evolution.

Язык: Английский

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Rapid and Efficient Detection of the SARS-CoV-2 Spike Protein Using an Electrochemical Aptamer-Based Sensor

ACS Sensors, Год журнала: 2021, Номер 6(8), С. 3093 - 3101

Опубликована: Авг. 10, 2021

The availability of sensors able to rapidly detect SARS-CoV-2 directly in biological fluids a single step would allow performing massive diagnostic testing track real time and contain the spread COVID-19. Motivated by this, here, we developed an electrochemical aptamer-based (EAB) sensor achieve rapid, reagentless, quantitative measurement spike (S) protein. First, demonstrated ability selected aptamer undergo binding-induced conformational change presence its target using fluorescence spectroscopy. Then, engineered work as bioreceptor EAB platform sensitivity specificity. Finally, demonstrate clinical potential sensor, tested it (serum artificial saliva), achieving rapid (minutes) single-step detection S protein range.

Язык: Английский

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Carbon-Based Nanomaterials: Promising Antiviral Agents to Combat COVID-19 in the Microbial-Resistant Era

ACS Nano, Год журнала: 2021, Номер 15(5), С. 8069 - 8086

Опубликована: Апрель 7, 2021

Therapeutic options for the highly pathogenic human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing current pandemic disease (COVID-19) are urgently needed. COVID-19 is associated with viral pneumonia and distress significant morbidity mortality. The proposed treatments have shown little or no effect in clinic so far. Additionally, bacterial fungal pathogens contribute to SARS-CoV-2-mediated complex. antibiotic resistance treatment increasing at an alarming rate. Therefore, carbon-based nanomaterials (CBNs), such as fullerene, carbon dots, graphene, their derivatives constitute a promising alternative due wide-spectrum antimicrobial activity, biocompatibility, biodegradability, capacity induce tissue regeneration. Furthermore, mode of action mainly physical (e.g., membrane distortion), characterized by low risk resistance. In this Review, we evaluated literature on antiviral activity broad-spectrum properties CBNs. CBNs had against 13 enveloped positive-sense single-stranded RNA viruses, including SARS-CoV-2. toxicity humans therapeutics complex other bacteria, fungi, those that multidrug-resistant.

Язык: Английский

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Cell entry by SARS-CoV-2

Trends in Biochemical Sciences, Год журнала: 2021, Номер 46(10), С. 848 - 860

Опубликована: Июнь 7, 2021

Both severe acute respiratory syndrome virus 2 (SARS-CoV-2) and SARS-CoV mainly invade human lungs, although increasing evidence shows that SARS-CoV-2 can also infect many other tissues to develop systematic infection multiple organ damage, hijack T cells directly paralyze host immunity.Angiotensin-converting enzyme (ACE2) is the major receptor for a crucial determinant cross-species transmission of virus; establish infections in panel domestic or wild animals via their ACE2 orthologs.Several proteins non-protein molecules have been found interact with S protein serve as potential alternative/auxiliary attachment receptors/coreceptors facilitate entry into specific types cells.Membrane fusion requires two proteolytic events by proteases, S1/S2 boundary harbors polybasic insertion expands spectrum available proteases thus tropism different tissues. Severe invades interacting receptors/coreceptors, well cofactors, its spike (S) further mediates between viral cellular membranes. The membrane protein, angiotensin-converting (ACE2), transmission. In addition, some auxiliary receptors cofactors are involved expand host/tissue SARS-CoV-2. After engagement, required cleave trigger fusogenic activity. Here we discuss recent advances understanding molecular during which will contribute developing vaccines therapeutics. late 2019 novel coronavirus named emerged humans, causes disease (COVID-19) [1.Coronaviridae Study Group International Committee on Taxonomy Viruses species syndrome-related coronavirus: classifying 2019-nCoV naming it SARS-CoV-2.Nat. Microbiol. 2020; 5: 536-544Crossref PubMed Scopus (2460) Google Scholar, 2.Zhou P. et al.A pneumonia outbreak associated new probable bat origin.Nature. 579: 270-273Crossref (7642) 3.Zhu N. from patients China, 2019.New Engl. J. Med. 382: 727-733Crossref (9884) 4.Wu F. China.Nature. 265-269Crossref (3658) Scholar]. This has rapidly developed worldwide pandemic resulted more than 0.1 billion confirmed cases 23 May 2021, including ~3.5 million deaths (www.who.int/emergencies/diseases/novel-coronavirus-2019). seventh human-infecting (HCoV) identified so far (Box 1), most similar 2002 [4.Wu Scholar,5.Zhong N.S. al.Epidemiology cause (SARS) Guangdong, People's Republic February, 2003.Lancet. 2003; 362: 1353-1358Abstract Full Text PDF (732) However, exhibits higher efficiency (see Glossary) compared HCoVs [6.Madewell Z.J. al.Household SARS-CoV-2: review meta-analysis.JAMA Netw. Open. 3e2031756Crossref (86) Scholar], relatively lower mortality rate Middle East (MERS-CoV) 7.Liu Z. al.The assessment latent period asymptomatic carriers infection.Int. Infect. Dis. 99: 325-327Abstract (12) 8.Zumla A. al.Middle syndrome.Lancet. 2015; 386: 995-1007Abstract (589) Although several candidate being distributed countries, global situation under control. It very urgent promote vaccination among populations effective therapeutics.Box 1Coronaviruses related epidemics/pandemicsCoronaviruses group enveloped viruses whose surface decorated proteins, resulting crown-shaped morphology. genome coronaviruses single-stranded positive-sense RNA an mRNA translation [11.V'Kovski al.Coronavirus biology replication: implications Rev. 19: 155-170Crossref (0) Coronaviruses belong order Nidovirales, family Coronaviridae, classified Orthocoronavirinae Letovirinae subfamilies. All (HCoVs) included subfamily Orthocoronavirinae, divided four genera, Alphacoronavirus, Betacoronavirus, Gammacoronavirus, Deltacoronavirus [9.Siddell S.G. al.Coronaviridae.Intervirology. 1983; 20: 181-189Crossref (55) So far, total seven identified. Among them, 229E, NL63, OC43, HKU1 commonly around world, mild symptoms such common cold fever. three, SARS-CoV, MERS-CoV, SARS-CoV-2, categorized highly pathogenic caused epidemics/pandemics countries.The first 229E reported 1960s (Figure I) [107.Tyrrell D.A. Bynoe M.L. Cultivation type common-cold cultures.Br. 1965; 1: 1467-1470Crossref Scholar,108.Hamre D. Procknow J.J. A isolated tract.Proc. Soc. Exp. Biol. 1966; 121: 190-193Crossref They often detected at same time usually do not lead symptoms. 2004 NL63 was discovered baby bronchiolitis Netherlands [109.van der Hoek L. al.Identification coronavirus.Nat. 2004; 10: 368-373Crossref (1155) year later Hong Kong, China elderly patient [110.Woo P.C. al.Characterization complete sequence coronavirus, HKU1, pneumonia.J. Virol. 2005; 79: 884-895Crossref (920) Since then, this world. case [5.Zhong epidemic spread over 30 countries ended 2003, 8000 infection, almost 800 deaths. MERS-CoV Saudi Arabia 2012 Asian [111.Zaki A.M. al.Isolation man Arabia.New 2012; 367: 1814-1820Crossref (2963) 2500 reported, ~850 died MERS-related disease, highest fatality (~35%) all HCoVs. were Wuhan, [3.Zhu led unprecedented ongoing affects As confirmed, 3.5 death cases. much those but seems be efficient populations. three thought originate animals, potentially natural host, bats [2.Zhou Scholar,112.Hu B. al.Bat origin coronaviruses.Virol. 12: 221Crossref (181) countries. large ~30 000 nt encodes classes proteins: polyproteins, pp1a pp1ab, cleaved 16 non-structural (NSPs) synthesis (and probably functions); structural (the spike, envelope, membrane, nucleocapsid proteins) essential assembly; nine accessory counteract immunity [10.Fehr A.R. Perlman S. Coronaviruses: overview replication pathogenesis.Methods Mol. 1282: 1-23Crossref Scholar,11.V'Kovski Viral step one important processes life cycle, key target process executed envelope recognizes cell allow released cytoplasm [12.Belouzard al.Mechanisms mediated protein.Viruses. 4: 1011-1033Crossref review, summarize functional studies entry, emphasis protein-mediated binding processes, factors coreceptors 1). An average 30–60 trimers protrude virion, distance 15 nm each [13.Yao H. al.Molecular architecture virus.Cell. 183: 730-738Abstract (139) 14.Ke al.Structures distributions intact virions.Nature. 588: 498-502Crossref (170) 15.Turonova al.In situ analysis reveals flexibility hinges.Science. 370: 203-208Crossref (135) Each trimeric ~10 length long helix stalk hinge allows adopt orientations [14.Ke Scholar,15.Turonova typical class I largest machine containing 1200 amino acid residues. During process, undergoes cleavage S1 S2 subunits remain assemble heterodimer 2) [16.Duan glycoprotein biosynthesis, structure, function, antigenicity: design spike-based vaccine immunogens.Front. Immunol. 11576622Crossref (46) Scholar,17.Walls A.C. al.Structure, antigenicity glycoprotein.Cell. 181: 281-292Abstract (2842) subunit N-terminal domain (NTD) C-terminal (CTD), latter responsible termed receptor-binding (RBD) [17.Walls 18.Wrapp al.Cryo-EM structure prefusion conformation.Science. 1260-1263Crossref (19) 19.Wang Q.H. al.Structural basis using ACE2.Cell. 894-904Abstract (890) 20.Lan al.Structure bound receptor.Nature. 581: 215-220Crossref (1531) 21.Shang recognition SARS-CoV-2.Nature. 221-224Crossref (1165) portion consists upstream (UH) region, peptide (FP), heptad repeat 1 (HR1), central (CD), (HR2), transmembrane (TM), cytoplasmic tail (CP) 2A,B). contrast FP located immediate N terminus subunit. Instead, shielded UH therefore second event expose [22.Matsuyama Protease-dependent mechanism coronaviruses.Uirusu. 2011; 61 (article Japanese): 109-116Crossref (1) Scholar,23.Walls al.Tectonic conformational changes fusion.Proc. Natl. Acad. Sci. U. 2017; 114: 11157-11162Crossref (218) Proteolysis S2′ site remove activating capacity triggers irreversible initiate [24.Fan X. post-fusion glycoprotein.Nat. Commun. 11: 3618Crossref (41) 25.Hoffmann M. al.SARS-CoV-2 depends TMPRSS2 blocked clinically proven protease inhibitor.Cell. 271-280Abstract (6278) 26.Cai Y. al.Distinct states protein.Science. 369: 1586-1592Crossref (207) Soon after outbreak, groups promptly 2002–2003 Scholar,25.Hoffmann Scholar] 3). ACE2, carboxypeptidase cleaves polypeptides renin/angiotensin system, cardiac function widely expressed various organs, suggesting [27.Kuba K. al.Multiple functions relevance cardiovascular diseases.Circ. 2013; 77: 301-308Crossref (96) Scholar,28.Yan R. full-length ACE2.Science. 1444-1448Crossref (1720) RBDs share high degree identity (74%) exhibit interaction profiles [19.Wang substitutions residues RBD atomic contacts affinity (~fourfold difference) 3C,D) property may human-to-human Scholar,7.Liu orthologs mammals cats, dogs, pigs, camels, horses, pangolins, bats, indicating SARS-CoV2 likely broad [29.Rodrigues al.Insights modeling.PLoS Comput. 16e1008449Crossref (5) Some closely pangolins Scholar,30.Xiao K.P. SARS-CoV-2-related Malayan pangolins.Nature. 583: 286-289Crossref (208) Two shown wide range bind mediate pseudotyped viruses, S-binding interface displays significant diversity 3E,F) [31.Liu al.Cross-species ACE2.Proc. 2021; 118e2020216118Crossref (2) Scholar,32.Wu al.Broad cat ACE2.Cell Discov. 6: 68Crossref (26) These findings strongly imply experienced spillover adaptation diverse determinants enabled host-jump across intermediate hosts finally allowed humans. Cryogenic electron microscopy (cryo-EM) determined structures conformations, both before Scholar,18.Wrapp Scholar,26.Cai complex [33.Benton D.J. al.Receptor priming fusion.Nature. 327-330Crossref (119) 34.Xu C. al.Conformational dynamics revealed cryo-EM.Sci. Adv. 7eabe5575Crossref (17) 35.Zhou T.Q. without reveal pH-dependent switch endosomal positioning domains.Cell Host Microbe. 28: 867-879Abstract snapshots enable deduction scenario 4). conformations state buried adjacent protomer (closed conformation) exposed access (open (Figures 2C 4A), known Scholar,36.Yuan glycoproteins dynamic domains.Nat. 8: 15092Crossref (342) within synchronized, implying asymmetric interactions receptor. study open transition closed make them accessible 4B) Therefore, 1–3 copies depending conformation individual Scholar,35.Zhou modulates local disrupt core, involves salt bridge contributed residue D614 Progressive dissociation head stalk, facilitates activation proteolysis 4C) Of note, variant harboring D614G substitution Europe mid-2020. mutation makes RB

Язык: Английский

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A systematic review of pregnant women with COVID-19 and their neonates

Archives of Gynecology and Obstetrics, Год журнала: 2021, Номер unknown

Опубликована: Апрель 2, 2021

In December 2019, a novel coronavirus disease (COVID-19) emerged in Wuhan, China, with an incredible contagion rate. However, the vertical transmission of COVID-19 is uncertain. This systematic review published studies concerning pregnant women confirmed and their neonates. We carried out search multiple databases, including PubMed, Web Science, Google Scholar, Scopus, WHO database using following keywords: (Coronavirus) OR (novel coronavirus) (COVID19) (COVID 19) (SARS-CoV2) (2019-nCoV)) ((pregnancy) (pregnant) (vertical transmission) (neonate) (newborn) (placenta) (fetus) (Fetal)). The took place April 2020. Original articles English were eligible if they included patients infected newborns. outcomes interest consisted clinical manifestations also effect on neonatal pregnancy outcomes. 37 involving 364 302 neonates included. vast majority third trimester pregnancy, only 45 cases first or second (12.4%). Most mothers described mild to moderate COVID-19. Of women, 25 asymptomatic at time admission. most common symptoms fever (62.4%) cough (45.3%). Two maternal deaths occurred. Some (12.1%) had negative SARS‐CoV‐2 test but displayed abnormalities computed tomography (CT) scan related COVID‐19. Twenty‐two (6.0%) developed severe pneumonia. occurred from pneumonia organ dysfunction. Studies total that provided data timing birth, there 65 (23.6%) preterm One baby was born dead mother who died babies alive COVID‐19, five newborns faced critical conditions, two later died. A 219 underwent nasopharyngeal specimen collection for SARS‐CoV‐2, which 11 tested positive (5%). Seventeen examined samples placenta, breast milk, umbilical cord, amniotic fluid, all except one fluid sample. confirm course resembles other populations. not sufficient evidence establish idea would complicate pregnancy.

Язык: Английский

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Neutralizing antibodies for the prevention and treatment of COVID-19

Cellular and Molecular Immunology, Год журнала: 2021, Номер 18(10), С. 2293 - 2306

Опубликована: Сен. 8, 2021

Abstract Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) initiates the infection process by binding to viral cellular receptor angiotensin-converting enzyme 2 through receptor-binding domain (RBD) in S1 subunit of spike (S) protein. This event is followed virus–cell membrane fusion mediated S2 subunit, which allows virus entry into host cell. Therefore, SARS-CoV-2 S protein a key therapeutic target, and prevention treatment coronavirus disease 2019 (COVID-19) have focused on development neutralizing monoclonal antibodies (nAbs) that target this In review, we summarize nAbs targeting proteins been developed date, with focus N-terminal RBD We also describe roles affinity, activity, protection provided these play COVID-19 discuss potential improve nAb efficiency against multiple variants. review provides important information for effective broad-spectrum activity current future strains.

Язык: Английский

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COVID-19 vaccines adverse events: potential molecular mechanisms

Immunologic Research, Год журнала: 2023, Номер 71(3), С. 356 - 372

Опубликована: Янв. 6, 2023

Язык: Английский

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The role of cell surface sialic acids for SARS-CoV-2 infection

Glycobiology, Год журнала: 2021, Номер 31(10), С. 1245 - 1253

Опубликована: Апрель 13, 2021

Abstract Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a new virus that has higher contagious capacity than any other previous human coronaviruses (HCoVs) and causes the current coronavirus disease 2019 pandemic. Sialic acids are group of nine-carbon acidic α-keto sugars, usually located at end glycans cell surface glycoconjugates serve as attachment sites for HCoVs. It therefore speculated sialic on host could co-receptors or factors SARS-CoV-2 entry well. Recent in silico modeling, molecular modeling predictions microscopy studies indicate potential acid binding by upon entry. In particular, flat acid-binding domain was proposed N-terminal spike protein, which may lead to initial contact interaction epithelium followed affinity angiotensin-converting enzyme 2 (ACE2) receptor, likely two-step fashion. However, recent vitro ex vivo ACE2 receptor confirmed an opposite role binding. neuraminidase treatment epithelial cells ACE2-expressing 293T increased Furthermore, glycosylation inhibition prevent ACE2–spike protein interaction. On hand, most study indicates gangliosides ligands receptor-binding protein. This mini-review discusses what been predicted known so far about infection future research perspective.

Язык: Английский

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The role of type I interferon in the treatment of COVID‐19

Journal of Medical Virology, Год журнала: 2021, Номер 94(1), С. 63 - 81

Опубликована: Сен. 1, 2021

Although significant research has been done to find effective drugs against coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2), no definite drug exists. Thus, now shifted towards immunomodulatory agents other than antivirals. In this review, we aim describe the latest findings on role of type I interferon (IFN)-mediated innate antiviral response SARS-CoV-2 and discuss use IFNs as a medication for COVID-19. A growing body evidence indicated promoting active but delayed Middle East in infected bronchial epithelial cells. Studies have demonstrated that IFNs' administration before viral peak inflammatory phase could offer highly protective effect. However, treatment during stages causes immunopathology long-lasting harm patients. Therefore, it is critical note best time window administration. Further investigation clinical effectiveness patients with mild COVID-19 its optimal timing route can be beneficial finding safe therapy disease.

Язык: Английский

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