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Coronavirus Epidemics and the Current COVID-19 Pandemic
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Aparna Bhardwaj, Prateek Kumar, Shivani Krishna Kapuganti, Vladimir N. Uversky, Rajanish Giri
The structural and accessory proteins are translation products of ~10 kb from the 3′ end one-third of the genome. The genes of these proteins are interspersed along the genome. As mentioned earlier, the structural proteins of SARS-CoV-2 are the S, E, M, and N proteins, and the ORFs code for accessory proteins ORF3a, ORF6, ORF7a, ORF8, ORF9, and ORF10, which are involved in the pathogenesis of the virus [40]. The structural proteins play crucial roles in pathogenesis, replication, viral packaging, and assembly [26]. Docking studies have shown that all four structural proteins interact with each other during their arrangement in the lipid bilayer [41]. The crystal structures of proteins from SARS-CoV and SARS-CoV-2 are presented in Figure 1.3.
Recent trends in next generation immunoinformatics harnessed for universal coronavirus vaccine design
Published in Pathogens and Global Health, 2023
Chin Peng Lim, Boon Hui Kok, Hui Ting Lim, Candy Chuah, Badarulhisam Abdul Rahman, Abu Bakar Abdul Majeed, Michelle Wykes, Chiuan Herng Leow, Chiuan Yee Leow
A substitution of aspartic acid with glycine at position 614 (D614G) found in the spike protein of SARS-CoV-2 was firstly discovered in February 2020. Scientists soon discovered that this mutation created a variant which was associated with enhanced infectivity. Within a few months, this variant dominated over the ancestral strain first identified in China, circulating extensively worldwide [50]. To date, five novel variants emerged notably as Variant of Concern (VOC), which are Alpha (UK variant B.1.1.7), Beta (South African variant B.1.351), Gamma (Brazilian variant P.1), Delta (Indian variant B.1.617.2) and Omicron (South African variant B.1.1.529). Needless to say, all of these variants contain D614G substitution in their S protein region. First of all, Alpha variant (B.1.1.7) was initially identified in the United Kingdom. Numerous mutations were observed in the regions including ORF1ab polyprotein, S protein, ORF8 protein and N protein. The S protein had several substitutions as well as deletions at positions 69 and 70 [51]. Substitution P681H is adjacent to the furin cleavage site, which is essential for viral infection [52] while deletion ∆69-70 increases viral infectivity and is associated with immune escape in immunocompromised patients [53]. It is noteworthy that ORF8 protein was truncated due to the presence of a stop codon. According to a preprint [54], Covaxin from Bharat Biotech is effective against Alpha variant.
Folic acid: a potential inhibitor against SARS-CoV-2 nucleocapsid protein
Published in Pharmaceutical Biology, 2022
Yu-meng Chen, Jin-lai Wei, Rui-si Qin, Jin-ping Hou, Guang-chao Zang, Guang-yuan Zhang, Ting-ting Chen
For the precise treatment of COVID-19, we performed molecular docking between drug compounds and viral proteins. The role of SARS-CoV-2 N is indispensable in RNA recognition, replication, transcription of the viral genome and modulation of the host immune response (Shan et al. 2021). The 3CL protease and NSP13 helicase are crucial for viral replication (Keum and Jeong 2012; Fernandes et al. 2019). The S proteins help infusing into the host, and the NSP9 replicase plays a major role in viral replication (Vaishali et al. 2020). The ORF3a protein can activate the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC (Siu et al. 2019). The ORF7A protein blocks cell cycle progression at the G0/G1 phase via the cyclin D3/pRb pathway (Schaecher et al. 2008). ORF8 can potentially mediate immune suppression and evasion activities (Flower et al. 2021). These proteins play an important role in viral host infection, so they are selected for molecular docking with the effective compounds obtained from the analysis. 3CL protease, ORF3a protein, and ORF8 have low binding energy with the compounds. The binding of SARS-CoV-2 N to folic acid was stable, indicating that it could be targeted for molecular therapy. Together, the above results show that the binding energy between folic acid and SARS-CoV-2 N is the lowest, so it was speculated that SARS-CoV-2 N might be the target of folic acid in COVID-19 treatment.
The chimera of S1 and N proteins of SARS-CoV-2: can it be a potential vaccine candidate for COVID-19?
Published in Expert Review of Vaccines, 2022
Amresh Kumar, Amit Ladha, Ankita Choudhury, Abu Md Ashif Ikbal, Bedanta Bhattacharjee, Tanmay Das, Gaurav Gupta, Chhavi Sharma, Adity Sarbajna, Subhash C Mandal, Manabendra Dutta Choudhury, Nahid Ali, Petr Slama, Nima Rezaei, Partha Palit, Onkar Nath Tiwari
After processing of the PP by main protease, 16 NSPs are produced, all of which perform vital functions by participating in the formation of different types of proteins involved in virus replication and transcription. Among these, NSP9 (dimeric form) is responsible for RNA-binding, a critical step during viral infection. Strategies for blocking the dimerization of NSP9 may be critical for preventing SARS-CoV-2 infection [31,32]. Pathogenesis of COVID-19 can also be triggered by the expression of novel proteins encoded by ORF3b and ORF8. Unlike ORF8, which does not have any known function, ORF3b is capable of inhibiting the expression of interferon (IFN)-β [33]. According to a structure modeling study, the endosome-associated-protein-like domain of NSP2 harbors a stabilizing mutation, which may explain why SARS-CoV-2 is more contagious than SARS-CoV-1. Additionally, the destabilizing mutation near the phosphatase domain of NSP3 may be indicative of an alternative pathogenic mechanism for SARS-CoV-2 [34].