Syncytia Formation in the Pathogenesis of SARS-CoV-2 Infection: Lessons from Viral Infections

It is widely known that numerous enveloped viruses can produce multinucleated cells (syncytia) as a result of viral entry-related membrane fusion events. By protecting the virus from the host’s immune reaction, these syncytia are thought to promote viral reproduction. Syncytia are collections of merged cells. A viral spike protein (S) on the surface of an infected cell interacts with receptors on nearby cells to cause the syncytia response. The innate immune system’s response to viruses affects how syncytia form. Some interferon-stimulated genes change the membrane in a way that reduces the likelihood of fusion. The severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus is quickly changing; also, several mutations occurred in its S protein. Individually and together, the Alpha, Beta, Gamma, and Delta variants carry mutations that significantly affect S function and syncytia formation. The function of syncytia in newly emerging variant diseases is still unknown, though. Syncytia could cause disease through promoting viral transmission, cytopathicity, immunological evasion, and inflammatory responses. The SARS-CoV-2 S protein variations include several changes that improve receptor interactions, fusogenicity, and antibody reactivity. A wide range of clinical symptoms, including moderate febrile sickness, severe respiratory distress, and occasionally deadly lung damage, can be brought on by an infection with SARS-CoV-2. Several of these lung illnesses (MERS-CoV) are linked to both the Middle East Respiratory Syndrome (MERS) and the severe acute respiratory syndrome coronavirus (SARS-CoV). Compared to acute respiratory syndromes, the lung thrombosis brought on by Coronavirus disease 2019 (COVID-19) is incredibly severe. In this review we focused on innate immunological elements that prevent syncytia from forming and the molecular triggers of S-mediated fusion.