SARS-CoV-2: Insight in genome structure, pathogenesis and viral receptor binding analysis – An updated review

Bhat, Eijaz Ahmed; Khan, Johra; Sajjad, Nasreena; Ali, Ahmad; Aldakeel, Fahad M.; Mateen, Ayesha; Alqahtani, Mohammed S.; Syed, Rabbani

doi:10.1016/j.intimp.2021.107493

Cited by 41 publications

(27 citation statements)

References 85 publications

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“…A recent report demonstrated acts as an antagonist of interferon (IFN) and viral encoded repressor of RNA interference 47 . Previous studies also reported N protein help package encapsidated genome into virions via binding Nps3 48 . Also, mutations were note in Nsp3 and Nsp5 which play role in blocking host innate immune response, promoting cytokine expression and inhibiting IFN signaling.…”

Section: Discussionmentioning

confidence: 92%

Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2

Sun

Cao

et al. 2020

Preprint

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The ongoing SARS-CoV-2 pandemic has brought an urgent need for animal models to study the pathogenicity of the virus. Herein, we generated and characterized a novel mouse-adapted SARS-CoV-2 strain named MASCp36 that causes acute respiratory symptoms and mortality in standard laboratory mice. Particularly, this model exhibits age and gender related skewed distribution of mortality akin to severe COVID-19, and the 50% lethal dose (LD50) of MASCp36 was ~100 PFU in aged, male BALB/c mice. Deep sequencing identified three amino acid mutations, N501Y, Q493H, and K417N, subsequently emerged at the receptor binding domain (RBD) of MASCp36, which significantly enhanced the binding affinity to its endogenous receptor, mouse ACE2 (mACE2). Cryo-electron microscopy (cryo-EM) analysis of mACE2 in complex with the RBD of MASCp36 at 3.7-angstrom resolution elucidates molecular basis for the receptor-binding switch driven by amino acid substitutions. Our study not only provides a robust platform for studying the pathogenesis of severe COVID-19 and rapid evaluation of coutermeasures against SARS-CoV-2, but also unveils the molecular mechanism for the rapid adaption and evolution of SARS-CoV-2 in mice.

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Section: Discussionmentioning

confidence: 92%

Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2

Sun

Cao

et al. 2020

Preprint

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“…Flavonoids such as quercetin, naringin, hesperetin, and catechin possess a higher grade of antiviral activity and they act by affecting the replication and infectivity of certain RNA and DNA viruses [ 125 ]. Recently, during this COVID-19 pandemic, there is an overwhelming scientific interest in searching for naturally occurring and synthetic flavonoid compounds to reduce COVID-19-infected cardiovascular malfunctioning by blocking the viral entry at the ACE2 receptor [ 126 ].…”

Section: Therapeutic Approaches and Future Drug Discoverymentioning

confidence: 99%

Dietary Flavonoids: Cardioprotective Potential with Antioxidant Effects and Their Pharmacokinetic, Toxicological and Therapeutic Concerns

et al. 2021

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Flavonoids comprise a large group of structurally diverse polyphenolic compounds of plant origin and are abundantly found in human diet such as fruits, vegetables, grains, tea, dairy products, red wine, etc. Major classes of flavonoids include flavonols, flavones, flavanones, flavanols, anthocyanidins, isoflavones, and chalcones. Owing to their potential health benefits and medicinal significance, flavonoids are now considered as an indispensable component in a variety of medicinal, pharmaceutical, nutraceutical, and cosmetic preparations. Moreover, flavonoids play a significant role in preventing cardiovascular diseases (CVDs), which could be mainly due to their antioxidant, antiatherogenic, and antithrombotic effects. Epidemiological and in vitro/in vivo evidence of antioxidant effects supports the cardioprotective function of dietary flavonoids. Further, the inhibition of LDL oxidation and platelet aggregation following regular consumption of food containing flavonoids and moderate consumption of red wine might protect against atherosclerosis and thrombosis. One study suggests that daily intake of 100 mg of flavonoids through the diet may reduce the risk of developing morbidity and mortality due to coronary heart disease (CHD) by approximately 10%. This review summarizes dietary flavonoids with their sources and potential health implications in CVDs including various redox-active cardioprotective (molecular) mechanisms with antioxidant effects. Pharmacokinetic (oral bioavailability, drug metabolism), toxicological, and therapeutic aspects of dietary flavonoids are also addressed herein with future directions for the discovery and development of useful drug candidates/therapeutic molecules.

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“…The positive‐sense ssRNA SARS‐CoV‐2 virus has a genome of about 29,700 nucleotides with 79.5% identity to SARS‐CoV‐1. Its genome encodes four main structural proteins; spike protein, membrane protein, nucleocapsid protein, and the envelope protein 6 , 7 . SARS‐CoV‐2 binds to angiotensin‐converting enzyme 2 (ACE2) via the (receptor‐binding domain) RBD of its spike protein that protrudes from the viral envelope.…”

Section: Introductionmentioning

confidence: 99%

A scalable and highly immunogenic virus‐like particle‐based vaccine against SARS‐CoV‐2

Mohsen

Baļķe

Zinkhan

et al. 2021

Allergy

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Background SARS‐CoV‐2 caused one of the most devastating pandemics in the recent history of mankind. Due to various countermeasures, including lock‐downs, wearing masks, and increased hygiene, the virus has been controlled in some parts of the world. More recently, the availability of vaccines, based on RNA or adenoviruses, has greatly added to our ability to keep the virus at bay; again, however, in some parts of the world only. While available vaccines are effective, it would be desirable to also have more classical vaccines at hand for the future. Key feature of vaccines for long‐term control of SARS‐CoV‐2 would be inexpensive production at large scale, ability to make multiple booster injections, and long‐term stability at 4℃. Methods Here, we describe such a vaccine candidate, consisting of the SARS‐CoV‐2 receptor‐binding motif (RBM) grafted genetically onto the surface of the immunologically optimized cucumber mosaic virus, called CuMV TT ‐RBM. Results Using bacterial fermentation and continuous flow centrifugation for purification, the yield of the production process is estimated to be >2.5 million doses per 1000‐litre fermenter run. We demonstrate that the candidate vaccine is highly immunogenic in mice and rabbits and induces more high avidity antibodies compared to convalescent human sera. The induced antibodies are more cross‐reactive to mutant RBDs of variants of concern (VoC). Furthermore, antibody responses are neutralizing and long‐lived. In addition, the vaccine candidate was stable for at least 14 months at 4℃. Conclusion Thus, the here presented VLP‐based vaccine may be a good candidate for use as conventional vaccine in the long term.

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SARS-CoV-2: Insight in genome structure, pathogenesis and viral receptor binding analysis – An updated review

Cited by 41 publications

References 85 publications

Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2

Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2

Dietary Flavonoids: Cardioprotective Potential with Antioxidant Effects and Their Pharmacokinetic, Toxicological and Therapeutic Concerns

A scalable and highly immunogenic virus‐like particle‐based vaccine against SARS‐CoV‐2

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