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Microstructure, pathophysiology, and potential therapeutics of COVID-19: A comprehensive review.

ABSTRACT: There have been over seven million cases and almost 413 372 deaths globally due to the novel coronavirus (2019-nCoV) associated disease COVID-19, as of 11 June 2020. Phylogenetic analysis suggests that there is a common source for these infections. The overall sequence similarities between the spike protein of 2019-nCoV and that of SARS-CoV are known to be around 76% to 78% and 73% to 76% for the whole protein and receptor-binding domain (RBD), respectively. Thus, they have the potential to serve as the drug and/or vaccine candidate. However, the individual response against 2019-nCoV differs due to genetic variations in the human population. Understanding the variations in angiotensin-converting enzyme 2 (ACE2) and human leukocyte antigen (HLA) that may affect the severity of 2019-nCoV infection could help in identifying individuals at a higher risk from the COVID-19. A number of potential drugs/vaccines as well as antibody/cytokine-based therapeutics are in various developmental stages of preclinical/clinical trials against SARS-CoV, MERS-CoV, and 2019-nCoV with substantial cross-reactivity, and may be used against COVID-19. For diagnosis, the reverse-transcription polymerase chain reaction is the gold standard test for initial diagnosis of COVID-19. A kit based on serological tests are also recommended for investigating the spread of COVID-19 but this is challenging due to the antibodies cross-reactivity. This review comprehensively summarizes the recent reports available regarding the host-pathogen interaction, morphological and genomic structure of the virus, and the diagnostic techniques as well as the available potential therapeutics against COVID-19.

SUBMITTER: Singh SP

PROVIDER: S-EPMC7361355 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundWhile Molnupiravir and Paxlovid have recently been approved for use in some countries, there are no widely available treatments for COVID-19, the disease caused by SARS-CoV-2 infection. Herbal extracts have been used to treat respiratory clinical indications by Ayurvedic medicine practitioners with minimal adverse reactions and intense research efforts are currently under way to develop some of these formulations for COVID-19 treatment.MethodsLiterature search for in silico, in vitro, in vivo, and clinical studies on the topic of Ayurvedic formulations for potential COVID-19 treatment, in order to present the current state of current knowledge by integrating information across all systems.ResultsThe search yielded 20 peer reviewed articles on in silico studies examining the interaction of phytoconstituents of popular Ayurvedic formulations with SARS-CoV-2 components and its receptors; five articles on preclinical investigations of the ability of selected Ayurvedic formulations to inhibit functions of SARS-CoV-2 proteins; and 51 completed clinical trials on the efficacy of using Ayurvedic formulations for treatment of mild to moderate COVID-19. Clinical data was available from 17 of the 51 trials. There was a considerable overlap between formulations used in the in silico studies and the clinical trials. This finding was unexpected as there is no clearly stated alignment between studies and the traditional pathway to drug discovery- basic discovery leading to in vitro and in vivo proof of concept, followed by validation in clinical trials. This was further demonstrated in the majority of the in silico studies where focus was on potential antiviral mechanisms, while the clinical trials were focused on patient recovery using oral treatments. In all 17 clinical trials where data was available, Ayurvedic treatments lead to a shorter period to recovery in participants with COVID-19.ConclusionThe most commonly used Ayurvedic treatments for management of respiratory symptoms associated with SARS-CoV-2 infection appear to have prophylactic and/or therapeutic properties. It would be of particular interest to assess synergistic and concomitant systemic effects and antiviral activities of individual phytoconstituents and their combinations in the Ayurvedic treatments.

Project description:BackgroundSARS-CoV-2 is a highly infectious respiratory virus associated with coronavirus disease (COVID-19). Discoveries in the field revealed that inflammatory conditions exert a negative impact on bone metabolism; however, only limited studies reported the consequences of SARS-CoV-2 infection on skeletal homeostasis. Inflammatory immune cells (T helper-Th17 cells and macrophages) and their signature cytokines such as interleukin (IL)-6, IL-17, and tumor necrosis factor-alpha (TNF-α) are the major contributors to the cytokine storm observed in COVID-19 disease. Our group along with others has proven that an enhanced population of both inflammatory innate (Dendritic cells-DCs, macrophages, etc.) and adaptive (Th1, Th17, etc.) immune cells, along with their signature cytokines (IL-17, TNF-α, IFN-γ, IL-6, etc.), are associated with various inflammatory bone loss conditions. Moreover, several pieces of evidence suggest that SARS-CoV-2 infects various organs of the body via angiotensin-converting enzyme 2 (ACE2) receptors including bone cells (osteoblasts-OBs and osteoclasts-OCs). This evidence thus clearly highlights both the direct and indirect impact of SARS-CoV-2 on the physiological bone remodeling process. Moreover, data from the previous SARS-CoV outbreak in 2002-2004 revealed the long-term negative impact (decreased bone mineral density-BMDs) of these infections on bone health.MethodologyWe used the keywords "immunopathogenesis of SARS-CoV-2," "SARS-CoV-2 and bone cells," "factors influencing bone health and COVID-19," "GUT microbiota," and "COVID-19 and Bone health" to integrate the topics for making this review article by searching the following electronic databases: PubMed, Google Scholar, and Scopus.ConclusionCurrent evidence and reports indicate the direct relation between SARS-CoV-2 infection and bone health and thus warrant future research in this field. It would be imperative to assess the post-COVID-19 fracture risk of SARS-CoV-2-infected individuals by simultaneously monitoring them for bone metabolism/biochemical markers. Importantly, several emerging research suggest that dysbiosis of the gut microbiota-GM (established role in inflammatory bone loss conditions) is further involved in the severity of COVID-19 disease. In the present review, we thus also highlight the importance of dietary interventions including probiotics (modulating dysbiotic GM) as an adjunct therapeutic alternative in the treatment and management of long-term consequences of COVID-19 on bone health.

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Microstructure, pathophysiology, and potential therapeutics of COVID-19: A comprehensive review.

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