Abstract
The coronavirus disease of 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global pandemic with increasing incidence and mortality rates. Recent evidence based on the cytokine profiles of severe COVID-19 cases suggests an overstimulation of macrophages and monocytes associated with reduced T-cell abundance (lymphopenia) in patients infected with SARS-CoV-2. The SARS-CoV-2 open reading frame 3 a (ORF3a) protein was found to bind to the human HMOX1 protein at a high confidence through high-throughput screening experiments. The HMOX1 pathway can inhibit platelet aggregation, and can have anti-thrombotic and anti-inflammatory properties, amongst others, all of which are critical medical conditions observed in COVID-19 patients. Here, we review the potential of modulating the HMOX1-ORF3a nexus to regulate the innate immune response for therapeutic benefits in COVID-19 patients. We also review other potential treatment strategies and suggest novel synthetic and natural compounds that may have the potential for future development in clinic.
Highlights
The ongoing coronavirus disease of 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection poses an unprecedented threat to public health as a global pandemic accompanied with high incidence of mortalities [1]
Most of the COVID-19 fatalities are due to respiratory failure caused by acute respiratory distress syndrome (ARDS) [2]
Previous studies have looked at the potency of drugs such as zotatifin, an inhibitor of a translation initiation factor, PB28, an agonist of the sigma-2 receptor and hydroxychloroquine, a quinoline derivative used as an anti-malarial, zotatifin was found to have the highest potency with an IC50 of 37 nanomolar [26]
Summary
The ongoing coronavirus disease of 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection poses an unprecedented threat to public health as a global pandemic accompanied with high incidence of mortalities [1]. Owing to a large spike recently, especially among the elderly population, it has become imperative to identify new safe and effective therapeutic strategies that include, but are not limited to, anti-viral therapy, vaccines and immune-modulating drugs [5]. Current treatment research strategies for COVID-19 are investigating several novel frontiers of therapeutics, such as the anti-viral drugs remdesivir, favilavir, the anti-malarial hydroxychloroquine, the anti-HIV drugs lopinavir, ritonavir and ACE2 inhibitor APN01 [6,7,8]. In spite of the immense investigational efforts being made for treating patients with COVID-19, additional therapeutic strategies are needed. Food and Drug Administration (FDA) and proving safety with efficacy in multi-arm clinical trials will take longer periods of time, delaying treatment to patients. The assemtbhlreodugvhirthioe nGsoalgrieatphpeanratruesletoastheedceexlltsruarcfaecleluvliaarslmy atlhl rvoeusicglehs.eTxhoecyastsoesmisbl[e1d0v–i1ri2on].s are released extracellularly through exocytosis [10,11,12]
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