Vaccines under development are thus mainly focusing on stimulating the host immune response, particularly to the S glycoprotein of SARS-CoV-2. mortality data, variability in response to contamination by the population, the nature of immunity and its duration, vaccine development issues, a fear that science might end up with excessive promises in response to COVID-19and were raised among scientists. Indeed, science may or may not deliver results in real time. In the presented paper we discuss some consequences of disease, its detection and serological tests, some solutions to disease prevention and management, pitfalls and obstacles, including vaccination. The presented ideas and data herein are meant to contribute to the ongoing debate on COVID-19 without pre-selection of available information. with 14 open reading frames (ORFs) encoding for 27 proteins. Its ABT-639 important feature is the spike glycoprotein (S) required for the virus binding to the host cell receptor ACE2. The S protein has the S1 domain, responsible for the receptor binding and the host virus range, while the S2 domain is responsible for cell membrane fusion. Specifically, SARS-CoV-2 has a receptor binding domain (RBD) within the S1 subunit that binds to ACE2 with a high affinity and is the main S1 subunit component that drives the SARS-CoV-2 binding to ACE2 [4]. Other SARS-CoV-2 structural proteins are the small envelope protein (E), matrix protein (M) and nucleocapsid protein (N) [5]. A cleavage domain in the S protein of SARS-CoV-2, named furin-cleavage domain, has not been previously reported in other SARS-CoV viruses. This S glycoprotein is cleaved by the host cell furin-like protease into S1 and S2 subunits [6] (Table 1). This SARS-CoV-2 spike protein has been suggested to be essential for the high transmissibility and infectivity of the virus observed at the beginning ABT-639 of the pandemic proclamation [7,8]. Currently, identified variants from Brazil, the United Kingdom and South Africa (see the subchapter below) have substantially higher binding affinity to ACE2 due to RBD mutations which confer to their increased transmissibility [9]. Table 1 Key differences between SARS-CoV-2 and its closest suggested relative RaTG13. with the viral sequence identified and designated as RmYNO2 showing a 93% homology to SARS-CoV-2 [18]. Some scientists demand for more research and further validation [19]. Both the natural zoonotic transfer or lab escape theories might partially explain the origin of the polybase cleavage site of furin, which is the area of the S glycoprotein that makes it susceptible to cleavage by the host enzyme furin and which greatly promotes the spread of the virus in the body. This novel furin place in SARS-CoV-2 is relevant in the infection process of humans, indeed distinguishing it from its closest relatives [7,20,21]. This explains the extreme affinity of the S glycoprotein virus for human receptors, which surprised virologists, also due to the SARS-CoV-2 unique adaptation to infect humans [22,23]. In summary, it is clear Rabbit Polyclonal to MRPL20 that science cannot yet give a conclusive answer to the question of the SARS-CoV-2 origin. SARS-CoV-2 New Variants Recent sequencing data show diverse SARS-Cov-2 sequence variants circulating globally. A Brazilian SARS-Cov-2 lineage B.1.1.28 known as P.1 (501Y.V3) has been for example, spreading and importing to other countries since February 2020 [26]. Besides, other studied variants include the SARS-Cov-2 lineage B.1.1.7 (501Y.V1) reported in the UK and other European countries and a variant from South Africa B.1.351 (501Y.V2) probably originating from the B.1.1.28 lineage. Both the B1.1.28. and B.1.351 display the mutation E484K relevant for the S protein activity [26]. According to the published data, the lineage B.1.1.7 accumulated 17 lineage-defining mutations as part of previous evolution and at the end of 2020 it accounted for 28% of SARS-CoV-2 infection in the UK [27]. Centers for Disease Control and Prevention (CDC) reports that the relevant mutation of this variant is ABT-639 identified in the receptor binding domain (RBD) of the S protein at position 501 but other mutations include 69/70 deletion in the S protein and P681H near the S1/S2 furin cleavage site. A mutation means that an actual change in sequence occurred. The viral genomes that accordingly differ in sequence are referred to as variants. A variant is a strain if a.