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Order Picornavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The further development of the plant-based FMDV vaccines was achieved during the work undertaken by the EC FP7 Plant Production of Vaccines (PLAPROVA) consortium, which investigated the use of transient expression technologies to produce VLPs of both human and veterinary pathogens—including FMDV—and was summarized by Thuenemann et al. (2013). Thus, the cleavage sites within the P1 polyprotein were modified to be recognized by the CPMV 24K protease, rather than the native FMDV 3C protease, since this was less toxic than 3C when expressed in plants (Saunders et al. 2009). In an attempt to express the empty FMDV capsids in plants, the P1 precursor and the CPMV 24K protease were coinfiltrated on separate constructs into N. benthamiana leaves. The modified P1 polyprotein carrying the recognition sites for 24K protease was expressed and processed into shorter proteins if the CPMV 24K protease was coexpressed. However, no VLP-like particles were observed by electron microscopy of protein samples isolated from agroinfiltrated plant leaves. This suggested that processing of the P1 polyprotein in plant cells and/or some steps of assembly of capsids differed from that occurring in animal cells. Alternatively, any empty capsids that did form might be unstable in plants, a plausible scenario given the acid-instability of FMDV capsids (Thuenemann et al. 2013).
Human Rhinovirus Infections
Published in Sunit K. Singh, Human Respiratory Viral Infections, 2014
Viral capsid-binding compounds, such as pleconaril, block virus uncoating in vitro.210,211 Clinical trials demonstrated significant reduction in duration of respiratory symptoms in individuals receiving pleconaril for naturally occurring colds, but the drug was not approved. Several low molecular weight compounds inhibit the 3C protease, which is essential for viral replication and assembly. In volunteer trials, a 3C-protease inhibitor, ruprintrivir, was found to reduce viral shedding, but was associated with blood-tinged mucus and irritation of the nasal passages.212
Antimicrobial peptides and other peptide-like therapeutics as promising candidates to combat SARS-CoV-2
Published in Expert Review of Anti-infective Therapy, 2021
Masoumeh Sadat Mousavi Maleki, Mosayeb Rostamian, Hamid Madanchi
Peptidomimetics are more stable and more resistant to digestion than peptides. They also have more powerful drug-like properties, for example, they have higher bioavailability than natural peptides and their ability to cross the blood-brain barrier has been improved. They also show more flexibility for changes and modifications. Pharmacokinetics studies have shown that the clearance of peptidomimetics is lower than natural peptides, so they have a longer half-life in the body [135]. In this regard, due to the high similarity of human rhinoviruses 3C protease with coronaviruses 3CL protease, the question arises as to what is the inhibitory efficiency of rupintrivir, a HRV 3C protease inhibitor peptidomimetic, on SARS-CoV-2 protease? Vatansever et al. found that rupintrivir was able to inhibit SARS-CoV-2 virus 3CL protease with maximal inhibitory concentration (IC50) of approximately 67 μM. They also showed that the serum stability of rupintrivir was higher than other drugs studied [136]. We suggest that researchers pay more attention to AVPs and other peptide-like compounds, especially those discussed in this review article, for basic and clinical research in the field of COVID-19 control. Regarding the emergence need to combat COVID-19, we also recommend focusing on available FDA-approved peptide therapeutics which could be promising candidates for drug development studies and clinical trials for COVID-19.
SARS, MERS and SARS-CoV-2 (COVID-19) treatment: a patent review
Published in Expert Opinion on Therapeutic Patents, 2020
José Adão Carvalho Nascimento Junior, Anamaria Mendonça Santos, Lucindo José Quintans-Júnior, Cristiani Isabel Banderó Walker, Lysandro Pinto Borges, Mairim Russo Serafini
Protease inhibitors are widely studied targets for the development of drugs against CoVs. Type 3C protease (3CLpro) is the main protease and structurally conserved among the types of CoVs [37]. Among the patents, several presented suggestions for inhibitors of this protease; as an example, Liu [38] developed a non-peptide SARS-CoV-1 3CLpro inhibitor derived from benzhydrylpiperazine. Its mechanism of action is based on the volume occupied by the compound that inhibits the hydrophobic interaction with the protease, presenting an inhibition rate of 45.3%. In another invention, Yang et al. [39], reported that sodium acamprosate had potent inhibitory activity against 3CLpro from SARS-CoV-1, presenting an inhibition rate greater than 85%.
Myocarditis: causes, mechanisms, and evolving therapies
Published in Expert Opinion on Therapeutic Targets, 2023
Tin Kyaw, Grant Drummond, Alex Bobik, Karlheinz Peter
Coxsackievirus encodes two distinct proteases, 2A (2Apro) and 3C (3Cpro), that cleave the polyprotein liberating mature proteins. During viral polyprotein processing, 2Apro is responsible for its own cleavage and all but one of the remaining cleavages are catalyzed by 3Cpro [155]. Although numerous 3C protease inhibitors have been developed to prevent Coxsackievirus infections, none has been approved for treating infections in humans [156]. In preclinical studies, 3C protease inhibitors are effective in preventing experimental murine myocarditis [157], but further, in particular, clinical studies are required.