# SARS-CoV-2 (COVID-19): New Discoveries and Current Challenges
## 2 Genomics and Virology  
CoVs (especially SARS-CoV-2) are a large enveloped non-segmented positive-sense, single-stranded RNA virus, that has caused enteric and respiratory illnesses in humans and/or animals [19]. SARS-CoV-2 is recognized to infect humans/animals, and the additional six CoVs comprise HCoV-229E, HCoV-OC43, HCoV-NL63, SARS-CoV, MERS-CoV, and HCoV-HKU [20]. Generally, HCoV-229E and -NL63 belong to \(\alpha\)-CoVs, and the others including SARS-CoV-2 have its place in the genus \(\beta\)-CoVs. Among these outbreaks, the two most known kinds of CoV, HCoV-229E, and HCoV-OC43, have generally caused a mild infection in people with adequate immune systems [21, 22]. All CoVs belong to a genus CoV with its excellent mutation rate in the Coronavirusiridae, and they all are large pleomorphic RNA viruses characteristically encompassing crown-shape peplomers or spikes with 80-160 nm in size and 27-32 kb positive polarity [5]. COVID-19 contains an RNA structure that belongs to the Coronavirusiridae family (Figure 3) [23]. Among the comparative genome sequences of SARS- and MERS-CoVs, COVID-19 has closer sequence identities with SARS-CoV. Genomic examination illustrates that novel SARS-CoV-2 is in the identical \(\beta\)-CoVs clades as SARS- and MERS-CoVs and can share a highly homological sequence with SARS-CoV, which also leads to acute, rapidly lethal pneumonia. Although the amino acid sequence of SARS-CoV-2 differs from other CoVs, particularly in the 1 ab polyprotein regions and surface glycoprotein or spike protein, all the seven CoVs encode a spike protein and surface glycoprotein that can easily bind to the host/cell receptor and thus can mediate viral entrance [26]. Well-known host receptors for \(\beta\)-CoVs contain ACE2 (angiotensin-converting enzyme-2) for SARS-CoV-2 as well as DPP4 (dipeptidyl peptidase-4) for MERS-CoV [27]. According to the SARS-CoV-2 intermediate host is still unclear and finding its probable intermediate host is essential to prevent further transmission of the epidemic. Cell entry is generally an imperative component of cross-species spread, particularly for the \(\beta\)-CoVs. A single region of the spike protein named the receptor-binding domain (RBD), also termed as C-terminal domain (CTD) can be mediated by the interaction with the host/cell receptor. SARS-CoV-2 is supposed to infect the host cells via the interaction between the angiotensin-converting enzyme 2 (ACE2) and the main amino acids of spike protein RBD which can act as the potential intermediate hosts spreading SARS-CoV-2 to animal/human, however, the specific mechanism is uncertain. In this respect, a study developed new approach to functionally test for the RBDs from lineage B \(\beta\)-CoVs in replacing the SARS-CoV spike-RBDs (Figure 4) [28]. Herein, biosynthesizing the RBD of spike sequences is much faster and cheaper than traditional pseudo typing approaches, which rely on the preparation of the full spike sequence (\(\sim\)4 kb) towards CoVs and is very cost prohibitive for the large panels of spikes. Besides that, lineage B RBDs can be divided into  
Figure 3: Naming of virus and its discovery; based on the illnesses current international classification [24]. Redrawn from Ref. [25], An Open Access article (CC BY 4.0). functionally separate clades and thus many formerly unappreciated viruses show compatibility with unrecognized receptors on human cells. In one study, samples obtained from seven patients with serious pneumonia were evaluated for determination of the causative pathogen; five examples were PCR-positive for CoVs. By focusing on PCR, a 29,891-base-pair coronavirus genome was obtained which shared 79.6% sequence identity to SARS-CoV BJ01 (GenBank-Rach accession number AY278488.2). High genome inclusion was acquired by remapping the entire reads of this genome and this sequence was analyzed; it was named novel coronavirus (2019-nCoV).