COVert IDentities of current worldwide pandemic.

Abstract

Recent decades have witnessed the emergence of several new devastating diseases caused by RNA viruses, including Ebola, Zika, Nipah, and Coronaviruses. Before 2002, coronaviruses were known to cause mild flu-like symptoms without causing any fatality. However, in 2002, sporadic emergence of infectious severe acute respiratory syndrome (SARS) killed around 750 people in several parts of world [1]. Later, it was reported that SARS was caused by SARS-Coronavirus (CoV), a type of coronavirus. In December 2019, a cluster of fatal, mysterious respiratory illnesses were caused by another strain of coronavirus (SARS-CoV-2) in Wuhan, China and it rapidly spreaded through an extensive air, ground, and sea transportation network. This epidemic spread all over the world and turned into a pandemic. As of the publication date, 88,387,352 people have been infected; 1,919,204 people have lost their lives globally, and there have been massive economic losses all over the world [2]. The disease is known as coronavirus (COVID-19) and the virus belongs to Betacoronavirus of family Coronaviridae. Members of Coronaviridae infect a broad range of avian and mammalian hosts, causing mild symptoms, but, sometimes, mutations can cause the virus to jump from an animal host to humans. Several members from this family of viruses have gained the capability of human-to-human transmission, and can cause widespread disease, such as SARS (2002), Middle East Respiratory Syndrome (MERS-2012), and the ongoing COVID-19. An analysis of the nucleotide sequences suggests that SARS-CoV-2 shares 79% similarity to SARS-CoV, 50% to MERS-CoV, and 96% to Bat CoV RaTG13, indicating that SARS-CoV-2 might have evolved from bat coronaviruses. Interestingly, despite the high similarity among these viruses, they are considerably different in the severity of clinical manifestations. All these viruses are transmitted while coughing or sneezing through droplet infection via respiratory route. The infection clinically presents with mild to severe flu-like symptoms. However, SARS-CoV-2 has a fatality rate of 2.3%, much lower than SARS-CoV (9.5%) and MERS-CoV (34.4%). SARS-CoV infection leads to high fever in most (97%) of the cases while only 43.1% SARS-CoV-2 patients showed fever higher than 37.5 °C [3]. This suggests that the low severity and often asymptomatic infections may facilitate disease spread and could be the reason behind the high rate of community transmission of this virus. SARS-CoV-2 is an enveloped, single-stranded, positive sense RNA virus. The genome is 29.9 kb packed inside a helical capsid made of nucleocapsid (N) protein, which is further encapsulated in an envelope formed by the envelope (E) protein and lipid bilayer derived from the host cell. Apart from nucleocapsid, envelope, and various nonstructural proteins, genomic RNA also encodes for membrane (M) and spike (S) proteins (Figure 1). The M and small envelope proteins (E) are involved in virus assembly, whereas the S protein facilitates virus entry into the cell by binding to angiotensin-converting enzyme (ACE) 2 receptors present on the host cell surface. As the spike protein plays a crucial role in the cell membrane fusion process, it also determines host tissue tropism and host range. Mutations in this region are giving rise to new and infectious/pathogenic strains. Three distinct variants of the virus have been identified: Ancestral type-A and mutated type-C variants are prevalent in Europe and the United States; type-B has spread in East Asian countries [4]. A new strain of SARS-CoV-2 has recently been identified during random genetic sequencing of positive COVID-19 samples in the United Kingdom. This strain has several mutations, but among them, N501Y mutation alters one of the six key residues in the receptor-binding domain (RBD) in the spike protein, making it up to 70% more transmissible among humans (Figure 2). Such mutations were predicted to happen, and several mutant strains might already be transmitting unnoticed. These mutations might lead to reinfections or could limit the efficacy of newly developed vaccines. Host immune response against SARS-CoV-2 starts upon virus entry into the epithelial cells of the respiratory