SARS-CoV-2 Intact Viral Particles

SARS-CoV-2 is a single-stranded RNA virus. The virus has four major structural proteins, including spike protein (S), membrane protein (M), envelope protein (E), and nucleocapsid protein (N), where the N protein helps to properly form the capsid and overall viral structure, and the S helps the virus attach to a host cell. SARS-CoV-2 is closely related to SARS-CoV, sharing approximately 79% of their genome, and both receptors are angiotensin-converting enzyme 2 (ACE2), making the pathogenesis of these two viral infections similar.

Figure 1. The structure and combination of COVID-19 virus and ACE2
(Source: Zhou H, et al. 2021)

SARS-CoV-2 is transmitted by respiratory droplets and aerosols. The incubation period after human infection is usually 4-5 days, and some infected people have no obvious symptoms, but most patients show mild to moderate respiratory illness with cough, fever, headache, myalgia and diarrhea. In severe cases, hypoxemia-induced dyspnea develops and some patients progress to progressive respiratory failure. COVID-19 patients with acute respiratory distress syndrome (ARDS) develop systemic hyperinflammation with elevated levels of proinflammatory cytokines and markers of inflammation such as interleukins, TNF, D-dimer and C-reactive protein (CRP). Therefore, close monitoring of serum levels of IL-6, IL-8 and TNF in hospitalized patients predicts disease progression and prognosis. In addition, patients with severe COVID-19 may have extrapulmonary disease manifested by gastrointestinal symptoms, acute cardiac, renal and hepatic injury, rhabdomyolysis, coagulopathy and shock.

There are no effective drugs for SARS-CoV-2, and drug repurposing is generally done by selecting effective drugs from existing drugs, which reduces the time and cost of drug discovery. Several antiviral drugs are available for the treatment of COVID-19, such as camostat, uminovir and ritonavir, a class of drugs that work primarily by preventing viral replication, thereby shortening the course of the disease and reducing the index of infection. Anti-inflammatory drugs are used to prevent tissue damage from cytokine storms. Anticoagulants are used to prevent thrombosis in a rational manner, depending on the patient's disease progression. Based on the fact that SARS-CoV2 enters host cells through ACE2 receptors, angiotensin-converting enzyme inhibitors (ACEIs) have been tried in the clinical treatment of COVID-19 and have been shown to reduce epithelial cell apoptosis, mesenchymal fibrosis, and collagen deposition, thereby reducing the incidence of lung injury. The use of ACEIs also reduces lung, kidney and heart damage caused by RAS overactivation. However, the drug requires attention to safety concerns.