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Integrated human/SARS-CoV-2 metabolic models present novel treatment strategies against COVID-19.

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic caused by the new coronavirus (SARS-CoV-2) is currently responsible for more than 3 million deaths in 219 countries across the world and with more than 140 million cases. The absence of FDA-approved drugs against SARS-CoV-2 has highlighted an urgent need to design new drugs. We developed an integrated model of the human cell and SARS-CoV-2 to provide insight into the virus' pathogenic mechanism and support current therapeutic strategies. We show the biochemical reactions required for the growth and general maintenance of the human cell, first, in its healthy state. We then demonstrate how the entry of SARS-CoV-2 into the human cell causes biochemical and structural changes, leading to a change of cell functions or cell death. A new computational method that predicts 20 unique reactions as drug targets from our models and provides a platform for future studies on viral entry inhibition, immune regulation, and drug optimisation strategies. The model is available in BioModels (https://www.ebi.ac.uk/biomodels/MODEL2007210001) and the software tool, findCPcli, that implements the computational method is available at https://github.com/findCP/findCPcli.

SUBMITTER: Bannerman BP

PROVIDER: S-EPMC8343166 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Bat sarbecovirus BANAL-236 is highly related to SARS-CoV-2 and infects human cells, albeit lacking the furin cleavage site in its spike protein. BANAL-236 replicates efficiently and pauci-symptomatically in humanized mice and in macaques, where its tropism is enteric, strongly differing from that of SARS-CoV-2. BANAL-236 infection leads to protection against superinfection by a virulent strain. We find no evidence of antibodies recognizing bat sarbecoviruses in populations in close contact with bats in which the virus was identified, indicating that such spillover infections, if they occur, are rare. Six passages in humanized mice or in human intestinal cells, mimicking putative early spillover events, select adaptive mutations without appearance of a furin cleavage site and no change in virulence. Therefore, acquisition of a furin site in the spike protein is likely a pre-spillover event that did not occur upon replication of a SARS-CoV-2-like bat virus in humans or other animals. Other hypotheses regarding the origin of the SARS-CoV-2 should therefore be evaluated, including the presence of sarbecoviruses carrying a spike with a furin cleavage site in bats.

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SARS-CoV-2 spike protein enhances MAP4K3/GLK-induced ACE2 stability in COVID-19

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| S-SCDT-EMM-2022-15904 | biostudies-other

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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019. It was first reported in Wuhan, China and has since become a global health concern. Keeping in view, the magnitude of the problem, scientists around the globe are working to develop effective therapeutic strategies. This review focuses on previous findings regarding SARS-CoV, which may prove helpful in future research on SARS-CoV-2. In addition, it also highlights recent developments in medicine and biotechnology toward developing effective drugs and vaccines against SARS-CoV-2. This review will analyze available data on this topic and will help researchers develop new thoughts using information already available as a step toward developing novel therapeutic strategies against SARS-CoV-2.

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2021-04-24 | GSE166424 | GEO

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Project description: Not available

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Comparative Evaluation of the Thermo Fisher TaqPath COVID-19 Combo Kit with the Cepheid Xpert® Xpress SARS-CoV-2 Assay for Detecting SARS-CoV-2 in Nasopharyngeal Specimens

Project description: Not available

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Project description:The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains to be a serious threat due to the lack of a specific therapeutic agent. Computational methods are particularly suitable for rapidly fight against SARS-CoV-2. This present research aims to systematically explore the interaction mechanism of a series of novel bicycloproline-containing SARS-CoV-2 Mpro inhibitors through integrated computational approaches. We designed six structurally modified novel SARS-CoV-2 Mpro inhibitors based on the QSAR study. The four designed compounds with higher docking scores were further explored through molecular docking, molecular dynamics (MD) simulations, free energy calculations, and residual energy contributions estimated by the MM-PBSA approach, with comparison to compound 23(PDB entry 7D3I). This research not only provides robust QSAR models as valuable screening tools for the development of anti-COVID-19 drugs, but also proposes the newly designed SARS-CoV-2 Mpro inhibitors with nanomolar activities that can be potentially used for further characterization to treat SARS-CoV-2 virus.

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Project description:Describe the transcriptomic profile of Golden Hamster olfactory bulb in response to SARS-CoV-2 infection, separating by sexes.

2021-06-19 | E-MTAB-10442 | biostudies-arrayexpress

Bee products as a source of promising therapeutic and chemoprophylaxis strategies against COVID-19 (SARS-CoV-2).

Project description:The emergence of novel coronavirus (SARS-CoV-2) in 2019 in China marked the third outbreak of a highly pathogenic coronavirus infecting humans. The novel coronavirus disease (COVID-19) spread worldwide, becoming an emergency of major international concern. However, even after a decade of coronavirus research, there are still no licensed vaccines or therapeutic agents to treat the coronavirus infection. In this context, apitherapy presents as a promising source of pharmacological and nutraceutical agents for the treatment and/or prophylaxis of COVID-19. For instance, several honeybee products, such as honey, pollen, propolis, royal jelly, beeswax, and bee venom, have shown potent antiviral activity against pathogens that cause severe respiratory syndromes, including those caused by human coronaviruses. In addition, the benefits of these natural products to the immune system are remarkable, and many of them are involved in the induction of antibody production, maturation of immune cells, and stimulation of the innate and adaptive immune responses. Thus, in the absence of specific antivirals against SARS-CoV-2, apitherapy could offer one hope toward mitigating some of the risks associated with COVID-19.

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