Coronaviruses are the diverse group of virus which infects domestic animals, birds as well as human . Coronaviruses are enveloped viruses which are the members of Coronaviridae family . Coronaviruses have positive strand RNA genome which is approximately 26–32 kb long. The overall structures of all coronaviruses are composed of the spike (S), envelope (E), membrane (M) and nucleocapsid (N) protein. The other non-structural proteins like RNA directed RNA polymerase, helicase, 3CL like proteinases etc are produced by the cleavage of replicase polyprotein 1ab or ORF 1ab polyprotein .
The first coronavirus 229E was identified in 1960. Since then different types of coronaviruses have emerged. HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63, HCoV-HKU1 and MERS-CoV are the coronaviruses which infect human . Most of the coronaviruses cause respiratory, enteric, hepatic, or neurological diseases with highly variable severity in their hosts . The first two coronavirus HCoV-229E and HCoV-OC43 infects lower respiratory tract where the later SARS-CoV, HCoV-NL63, HCoV-HKU1 infect both lower and upper respiratory tract [4, 6–8]. But the newly emerged MERS-CoV infects both lung and kidney that reflects how these viruses are changing their cell tropism and becoming highly pathogenic .
Most infections caused by human coronaviruses were relatively mild. Among all the human coronaviruses, SARS-CoV and MERS-CoV are much more deadly. The severe acute respiratory syndrome (SARS) outbreak caused by SARS-CoV in 2002 to 2003. The SARS-CoV created outbreak resulted in a total of 916 deaths among more than 8000 confirmed cases in over 30 countries [10, 11]. The newly emerged MERS-CoV is now posing a great threat for human. According to WHO, 75 people have died among more than 178 confirmed cases caused by MERS-CoV . Though this MERS-CoV virus was first found in Saudi Arabia 2012, now it has been emerged in UK, France, Tunisia, Spain and Italy that indicates it’s going to create another outbreak like SARS-CoV [12–14]. From 1960 to till now there is no recommended drug or vaccine for MERS-CoV infection and treatment relies on exclusively supportive care, which gives the high case-fatality rate, is not highly effective .
In 2003 after the discovery of SARS-CoV, there were a significant increase in research on coronavirus, but no definitive antiviral or therapeutic treatment for coronavirus infections came from these researches . From the clinical experience of SARS-CoV found that a number of interventions including ribavirin with and without corticosteroids, ribavirin with protease inhibitors and interferon with corticosteroids may improve outcome. But a definitive treatment was not clearly established and the therapeutic interventions have not been evaluated in vivo.
The identification of therapeutics is a high priority and though there is currently no specific therapy or vaccine for human coronaviruses, this disease has been severe with a high case-fatality rate . As these viruses are now becoming pathogenic and causing outbreaks, so steps have to be taken to prevent human death. Vaccination is one of the most efficient ways to prevent infectious disease . Effective vaccines controlling virus spread and disease are available for a number of infections, such as smallpox, poliomyelitis, measles, mumps, rubella, influenza, hepatitis A, and hepatitis B . For coronavirus, this vaccine approach is hindered by the fact that human coronavirus strains are not structurally related and they are changing rapidly by recombination . Therefore, designing a universal vaccine against conserved regions for all human coronaviruses is a major challenge at present.
With the disclosure of huge sequence information, epitope based vaccine design now has become a most promising approach for viral vaccine preparation . In order to prepare vaccines, computational prediction of epitopes and vaccine design can reliably aid this process to reduce time and cost. Although the epitope based vaccine design is now a familiar concept, not much work has been done in case of coronaviruses.
In this study, we design an epitope based universal vaccine which can be use to prevent all kind of human coronaviruses. For this, bioinformatics analyses of viral proteins were done for finding the conserved peptide region and for mapping the evolutionary conserved epitope. The 3D structure of RNA directed RNA polymerase was determined by threading modeling technique and a highly immunogenic, accessible and conserved epitope was identified. This epitope can be used as a universal vaccine against all human coronaviruses.