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COVID-19 Pandemic and Traditional Chinese Medicines
Published in Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga, The Covid-19 Pandemic, 2023
Roheena Abdullah, Ayesha Toor, Hina Qaiser, Afshan Kaleem, Mehwish Iqtedar, Tehreema Iftikhar, Muhammad Riaz, Dou Deqiang
Curcumin is phenolic compound that is present in extract of Turmeric rhizome and has anti-viral, -oxidant, -inflammatory, and -cancerous actions. With its dose from 3.3 to 10 μmol/L, it plays inhibitory role on replication of SARS-CoV particles and at IC50 of 40 μmol/L, it has an inhibitory effect on 3C like protease. Curcumin is also responsible for blocking cytokine storm by blocking the release of cytokines such as IL-1 and -6 and TNF-α, during patient treatment. Molecular docking using virtual screening showed the affinity of curcumin for PLpro, protease domain of ACE 2 receptor (PD-ACE 2) and RBD of spike glycoprotein (RBD-S) that can prohibit the interaction between viral and ACE 2 domains [24].
Noroviruses: Laboratory Surrogates for Determining Survival and Inactivation
Published in Dongyou Liu, Laboratory Models for Foodborne Infections, 2017
Doris H. D’Souza, Snehal S. Joshi
NoVs are small viruses about 27–32 nm in size and round in structure with an icosahedral symmetry. The human norovirus (HNoV) genome contains a single-stranded positive-sense RNA about 7.6 kb in length that is enclosed in a capsid without an envelope [3]. The capsid is made of 90 capsomers protruding from the shell that has 90 dimers of capsid protein. The genome has three open reading frames (ORFs). ORF1 (nucleotides 146–5359) is about 5 kb in size and encodes a ∼200 kDa nonstructural polyprotein. This nonstructural protein is cleaved to produce the N-terminal protein, the enzyme nucleoside triphosphatase, a 3A-like protein, a genome-linked viral protein (VpG), a 3C-like protease, and RNA-dependent RNA-polymerase (RdRp) [4]. ORF2 (nucleotides 5346–6935) is ∼1.8 kb in size and encodes the 57 kDa major structural capsid viral protein VP1; ORF3 (nucleotides 6938–7573) is ∼0.6 kb in size and encodes a small 22 kDa minor viral structural protein, VP2, reported to package the genome into virions [5,6]. The NoV genus at the time of this submission, is composed of five genogroups based on sequence analysis: genogroup I (GI) (prototype Norwalk virus); GII (prototype Snow Mountain virus); GIII (prototype bovine enteric calicivirus); GIV (prototype Alphatron and Ft. Lauderdale viruses); and GV (prototype Murine NoV) [7,8].
Human Coronavirus Respiratory Infections
Published in Sunit K. Singh, Human Respiratory Viral Infections, 2014
Thomas Edward Cecere, Stephanie Michelle Todd, Owen Benjamin Richmond
Some advancement has been made with regard to identifying potential antiviral candidates, most of which target the S protein, nsp 13 helicase, or the 3C-like protease (3CLpro). Synthetic peptides that competitively bind S protein can inhibit viral entry by preventing the conformational changes necessary for S protein during viral fusion.64,65 Lectins, and other substances that bind carbohydrates, can diminish infection by binding viral glycoproteins like S protein and creating steric hindrance during attachment, fusion, and entry.64 The efficacy of lectins as a therapeutic route depends upon the amount of glycosylation present on the host cell, which can vary depending upon the cell type infected.64
An overview of the recent progress in Middle East Respiratory Syndrome Coronavirus (MERS-CoV) drug discovery
Published in Expert Opinion on Drug Discovery, 2023
MERS 3C-like protease (3CLpro), also known as main protease (Mpro), is included in the processing of the virus polyproteins. Like MERS-PLpro, MERS-3CLpro has a crucial role in the replication of the virus, so 3CLpro can be an excellent target for novel drugs [73, 90, 91]. It is a cysteine protease with two N-terminal domains, and its active sites reside in the cleft between the two domains. MERS-3CLpro does not have a single active site but has several subsites from S1 to S6 [31]. New α-ketoamides, such as the SARS-CoV-2/MERS Mpro inhibitors with broad-spectrum activity, had IC50 values in the low micromolar range [92]. Four compounds (9a, 9c, 9d, and 9e) inhibited the protease with IC50 values of less than 21 µM, while two compounds (9c and 9d) had Mpro inhibition values in the submicromolar range. Compounds 9c and 9d, as covalent reversible inhibitors of SARS/MERS Mpro, had IC50 values of 60 and 70 nM, respectively.
Myocarditis: causes, mechanisms, and evolving therapies
Published in Expert Opinion on Therapeutic Targets, 2023
Tin Kyaw, Grant Drummond, Alex Bobik, Karlheinz Peter
SARS-CoV-2 expresses two viral proteases that are essential for replication: main protease (Mpro) or 3C-like protease (3CLpro) and papain-like protease (PLpro) which are equally important. A large variety of 3CLpro inhibitory compounds have been developed [149] and one, Nirmatrelvir is available for treating high-risk adults with COVID-19 [150]; others are in clinical trials [151]. Recently, the question of resistance to nirmatrelvir has been examined, raising the possibility that combination therapy rather than monotherapy should be considered to minimize the likelihood of SARS-CoV-2 escape [152]. In contrast to 3CLpro, PLpro is important in both the cleaving viral polyproteins and of the ubiquitin-like interferon-stimulated gene 15 protein (ISG15) from interferon responsive factor 3 (IRF3), thus attenuating type 1 interferon viral responses [153]. It raises the possibility that inhibitors of PLpro may be more beneficial because they also enable antiviral mechanisms. High throughput screenings have identified a few potential PLpro inhibitors [154].
Ligand-based discovery of coronavirus main protease inhibitors using MACAW molecular embeddings
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Jie Dong, Mihayl Varbanov, Stéphanie Philippot, Fanny Vreken, Wen-bin Zeng, Vincent Blay
A variety of medicinal targets to fight infection by SARS-CoV-2 are being investigated8,9, and the main viral protease Mpro is particularly promising. After the virus infects and enters a human host cell, the two main ORF1a/b of its RNA genome first translate and express two polyprotein precursors (pp1a and pp1ab) with the help of the host cell machinery10–14. The polyprotein precursor undergoes intramolecular cleavage under the action of the main protease of SARS-CoV-2, Mpro (also known as 3C-like protease or 3CLpro), and the papain-like protease, PLpro, to produce multiple non-structural proteins (Nsps), Nsp1 to Nsp16. Some of the non-structural proteins produced participate in the production of viral subgenomic RNA encoding the four major structural proteins (Envelope/E protein, Membrane/M protein, Spike/S protein, and Nucleocapsid/N protein), which are needed to complete the reproduction and release of progeny viruses10–14.