Precision therapeutic targets for COVID-19

Abstract

Beginning in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a novel pathogen that causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 has infected more than 111 million people worldwide and caused over 2.47 million deaths. Individuals infected with SARS-CoV-2 show symptoms of fever, cough, dyspnea, and fatigue with severe cases that can develop into pneumonia, myocarditis, acute respiratory distress syndrome, hypercoagulability, and even multi-organ failure. Current clinical management consists largely of supportive care as commonly administered treatments, including convalescent plasma, remdesivir, and high-dose glucocorticoids. These have demonstrated modest benefits in a small subset of hospitalized patients, with only dexamethasone showing demonstrable efficacy in reducing mortality and length of hospitalization. At this time, no SARS-CoV-2-specific antiviral drugs are available, although several vaccines have been approved for use in recent months. In this review, we will evaluate the efficacy of preclinical and clinical drugs that precisely target three different, essential steps of the SARS-CoV-2 replication cycle: the spike protein during entry, main protease (MPro) during proteolytic activation, and RNA-dependent RNA polymerase (RdRp) during transcription. We will assess the advantages and limitations of drugs that precisely target evolutionarily well-conserved domains, which are less likely to mutate, and therefore less likely to escape the effects of these drugs. We propose that a multi-drug cocktail targeting precise proteins, critical to the viral replication cycle, such as spike protein, MPro, and RdRp, will be the most effective strategy of inhibiting SARS-CoV-2 replication and limiting its spread in the general population.

Annexin A1 as a potential prognostic biomarker for COVID‐19 disease: Case–control study

“…In addition to the present study, many mechanisms have been proposed as therapeutic targets in COVID-19 infection. 36 In a hypothesis published Moreover, this study found 69.8% sensitivity and 58.1% specificity at 17.2 ng/ml serum level of AnxA1 in order to predict the need for ICU treatment in patients admitted to ED, suggesting that serum AnxA1 level may be a useful biomarker in predicting the need for ICU treatment.…”

“…In addition to the present study, many mechanisms have been proposed as therapeutic targets in COVID‐19 infection. 36 In a hypothesis published by Bonavita, it was suggested that the Ac2‐26 mimetic protein of the AnxA1 protein could be a therapeutic target, especially in the treatment of severe COVID‐19 infection, and this peptide could be one of the main mediators of cytokine storm syndrome by lowering IL‐6 levels. 14 Additionally, the use of exogenous corticosteroids (especially dexamethasone) in severe/critical COVID‐19 infection has also been recommended by WHO guidelines for COVID‐19 treatment and has been put into clinical practice.…”

COVID-19 Management Missteps

“…This type of therapy includes, for example, staying hydrated, social distancing, and monitoring vitals at home for people with mild symptoms. For more serious cases, measures include supplemental oxygen and mechanical ventilatory support, which may be needed for more severe cases [13]. Furthermore, since the beginning of the pandemic, various drugs have been examined for the potential treatment of COVID-19.…”

Conserved recombination patterns across coronavirus subgenera

“…It is considered a class I fusion protein in that it contains both a receptor-binding domain (called S1) and a domain for mediating the membrane fusion process (called S2) (White et al 2008;Xia et al 2020). The Spike of SARS-CoV-2 has become a target in the development of vaccines and therapeutic drugs for COVID-19, due both to its importance during the viral infection cycle and to its being the primary target of host immune responses (Krumm et al 2021).…”