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Host-pathogen interaction in COVID-19: Pathogenesis, potential therapeutics and vaccination strategies.

ABSTRACT: The current coronavirus pandemic, COVID-19, is the third outbreak of disease caused by the coronavirus family, after Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome. It is an acute infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This severe disease is characterised by acute respiratory distress syndrome, septic shock, metabolic acidosis, coagulation dysfunction, and multiple organ dysfunction syndromes. Currently, no drugs or vaccines exist against the disease and the only course of treatment is symptom management involving mechanical ventilation, immune suppressants, and repurposed drugs. The severe form of the disease has a relatively high mortality rate. The last six months have seen an explosion of information related to the host receptors, virus transmission, virus structure-function relationships, pathophysiology, co-morbidities, immune response, treatment and the most promising vaccines. This review takes a critically comprehensive look at various aspects of the host-pathogen interaction in COVID-19. We examine the genomic aspects of SARS-CoV-2, modulation of innate and adaptive immunity, complement-triggered microangiopathy, and host transmission modalities. We also examine its pathophysiological impact during pregnancy, in addition to emphasizing various gaps in our knowledge. The lessons learnt from various clinical trials involving repurposed drugs have been summarised. We also highlight the rationale and likely success of the most promising vaccine candidates.

SUBMITTER: Varghese PM

PROVIDER: S-EPMC7434692 | 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.

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Host-pathogen interaction in COVID-19: Pathogenesis, potential therapeutics and vaccination strategies.

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