Pathomechanisms, therapeutic targets and potent inhibitors of some beta-coronaviruses from bench-to-bedside
| Autor: | Yusuf Oloruntoyin Ayipo, Sani Najib Yahaya, Mohd Nizam Mordi, Waleed Abdullah Ahmad Alananzeh, H. F. Babamale |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Microbiology (medical) MAPK/ERK pathway Drug targets Coronaviridae 030106 microbiology Review Therapeutic design Resveratrol Pharmacology Microbiology Pathophysiology Antiviral Agents Multi-target pharmacology Coronavirus OC43 Human 03 medical and health sciences chemistry.chemical_compound Viral Proteins Chloroquine Genetics medicine Humans Receptor Molecular Biology Protein kinase B Furin Ecology Evolution Behavior and Systematics PI3K/AKT/mTOR pathway Randomized Controlled Trials as Topic biology Kinase SARS-CoV-2 Coronavirus 030104 developmental biology Infectious Diseases chemistry Biochemical analysis Host-Pathogen Interactions biology.protein Middle East Respiratory Syndrome Coronavirus Coronavirus Infections medicine.drug |
| Zdroj: | Infection, Genetics and Evolution |
| ISSN: | 1567-7257 1567-1348 |
| Popis: | Since the emergence of their primitive strains, the complexity surrounding their pathogenesis, constant genetic mutation and translation are contributing factors to the scarcity of a successful vaccine for coronaviruses till moment. Although, the recent announcement of vaccine breakthrough for COVID-19 renews the hope, however, there remains a major challenge of accessibility to urgently match the rapid global therapeutic demand for curtailing the pandemic, thereby creating an impetus for further search. The reassessment of results from a stream of experiments is of enormous importance in identifying bona fide lead-like candidates to fulfil this quest. This review comprehensively highlights the common pathomechanisms and pharmacological targets of HCoV-OC43, SARS-CoV-1, MERS-CoV and SARS-CoV-2, and potent therapeutic potentials from basic and clinical experimental investigations. The implicated targets for the prevention and treatment include the viral proteases (Mpro, PLpro, 3CLpro), viral structural proteins (S- and N-proteins), non-structural proteins (nsp 3, 8, 10, 14, 16), accessory protein (ns12.9), viroporins (3a, E, 8a), enzymes (RdRp, TMPRSS2, ADP-ribosyltransferase, MTase, 2'-O-MTase, TATase, furin, cathepsin, deamidated human triosephosphate isomerase), kinases (MAPK, ERK, PI3K, mTOR, AKT, Abl2), interleukin-6 receptor (IL-6R) and the human host receptor, ACE2. Notably among the 109 overviewed inhibitors include quercetin, eriodictyol, baicalin, luteolin, melatonin, resveratrol and berberine from natural products, GC373, NP164 and HR2P-M2 from peptides, 5F9, m336 and MERS-GD27 from specific human antibodies, imatinib, remdesivir, ivermectin, chloroquine, hydroxychloroquine, nafamostat, interferon-β and HCQ from repurposing libraries, some iron chelators and traditional medicines. This review represents a model for further translational studies for effective anti-CoV therapeutic designs. |
| Databáze: | OpenAIRE |
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