57.1%) [123]. drugs is limited, and data on efficacy for the new indication are not strong. Overall, the response of the global scientific community to the COVID-19 pandemic has been impressive, as evident from the volume of scientific literature elucidating the molecular biology and pathophysiology of SARS-CoV-2 and the approval of three new drugs for clinical management. Reviewed studies have shown mixed data on efficacy and safety of the currently utilized drugs. The lack of standard treatment for COVID-19 has made it difficult to interpret results from most of the published studies due to the risk of attribution error. The long-term effects of drugs can only be assessed after several years of clinical experience; therefore, the efficacy and safety of current COVID-19 therapeutics should continue to be rigorously monitored as part of post-marketing studies. are large, enveloped, single-stranded RNA viruses found in both humans and various (±)-Epibatidine animal species. Their distinctive corona or crown-like morphology visualized by electron microscopy is due to the presence of spike-like glycoproteins emanating from the surface of the viral envelope [4,5]. Coronaviruses are broadly categorized into four genera: alpha-CoV, beta-CoV, gamma-CoV, and delta-CoV [6,7]. As with MERS-CoV and SARS-CoV, SARS-CoV-2 is classified as a beta-CoV and is characterized by viral genetic diversity, genomic plasticity, and multiple host adaptability due to high mutation rates [8]. Coronaviruses belonging to the alpha-CoV and beta-CoV genera are transmissible to humans, and genome similarity evidence indicates that (±)-Epibatidine these viruses originated from bats, although the pangolin has been suggested to be an intermediate host for human contamination by SARS-CoV-2 [9,10,11,12,13,14]. The primary mode of SARS-CoV-2 transmission is through respiratory droplets expelled during face-to-face (±)-Epibatidine exposure, although spread via contact with contaminated surfaces is also possible [15]. Infectivity is dependent upon three structural proteins (E, M, and S) in the viral envelope that have critical functions in the replication cycle of SARS-CoV-2 [16]. Envelope (E) proteins form viroporins, or ion channels, in the lipid bilayer and are important for viral maturation [17]. Membrane (M) proteins play essential roles in the morphogenesis and assembly of new SARS-CoV-2 progeny by interacting with other structural proteins [18]. The spike (S) is usually a surface-exposed glycoprotein that is essential for SARS-CoV-2 attachment, fusion, and entry into the host cell [19]. Contamination is initiated by binding of the spike glycoprotein to the human angiotensin-converting enzyme 2 (hACE2) receptor on SARS-CoV-2 target cells, such as nasal and bronchial epithelial (±)-Epibatidine cells and pneumocytes [20]. The dissemination of SARS-CoV-2 contamination to extra-pulmonary sites in COVID-19 patients is due to the wide cellular distribution of the hACE2 receptor, which is also found on tissues of the gastrointestinal tract, cardiovascular, urogenital, and central nervous systems Rabbit Polyclonal to CDC25A [21]. Cleavage of the S protein by the host cell-associated transmembrane protease serine 2 (TMPRSS2) activates the S2 domain name for fusion of the viral envelope with the cell membrane, permitting entry of the viral nucleocapsid [20]. SARS-CoV-2 contamination is characterized by variable clinical severity. The clinical picture of COVID-19 ranges widely from asymptomatic or moderate cold-like symptoms to acute respiratory distress syndrome (ARDS), respiratory failure, multiple organ failure, and death. The most common presenting features in adults are fever (up to 90%), dry cough (60C86%), shortness of breath (53C80%), fatigue (38%), myalgia (15C44%), sputum production (33%), sore throat (13.9%), and headache (13.6%) [22,23,24,25]. Nonclassical gastrointestinal symptoms such as diarrhea (3.8%) and vomiting (5.0%) occur infrequently [26]. In addition, a majority of reported COVID-19 cases (64C80%) also presented with ageusia and anosmia [27,28]. Clinical evidence suggests that dysregulated and excessive proinflammatory cytokine release (a cytokine storm) constitutes a major cause of ARDS and is associated with severe health deterioration in critically ill COVID-19 patients (reviewed in Ye et al., 2020 [29]). A poor prognosis from COVID-19 is usually disproportionately higher among individuals of advanced age and who have pre-existing chronic medical conditions. Hospital mortality is usually less than 5% for COVID-19 patients who are younger than 40 years, while the hospital death rate rises substantially to 35% for 70- to 79-year-old patients, and to 60% for 80- to 89-year-old patients [23]. The potential long-term health impacts in survivors of severe COVID-19 currently remain unknown. Therapeutics for the prevention and management of SARS-CoV-2 infection have.