Vaccine development and therapeutic design for 2019-nCoV/SARS-CoV-2: Challenges and chances

Abstract

The ongoing outbreak of the recently emerged 2019 novel coronavirus (nCoV), which has seriously threatened global health security, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high morbidity and mortality. Despite the burden of the disease worldwide, still, no licensed vaccine or any specific drug against 2019-nCoV is available. Data from several countries show that few repurposed drugs using existing antiviral drugs have not (so far) been satisfactory and more recently were proven to be even highly toxic. These findings underline an urgent need for preventative and therapeutic interventions designed to target specific aspects of 2019-nCoV. Again the major factor in this urgency is that the process of data acquisition by physical experiment is time-consuming and expensive to obtain. Scientific simulations and more in-depth data analysis permit to validate or refute drug repurposing opportunities predicted via target similarity profiling to speed up the development of a new more effective anti-2019-nCoV therapy especially where in vitro and/or in vivo data are not yet available. In addition, several research programs are being developed, aiming at the exploration of vaccines to prevent and treat the 2019-nCoV. Computational-based technology has given us the tools to explore and identify potentially effective drug and/or vaccine candidates which can effectively shorten the time and reduce the operating cost. The aim of the present review is to address the available information on molecular determinants in disease pathobiology modules and define the computational approaches employed in systematic drug repositioning and vaccine development settings for SARS-CoV-2.

Keywords: COVID-19; SARS-CoV-2; bioinformatics; drug target; treatment; vaccine.

Figure 1

The putative neutralizing and infection‐enhancing antibody response to human SARS‐CoV‐2 virus infection. The host's immune response elicited by either natural infection or vaccination targeting a surface antigen influences the proliferative activity of live virus through antibody‐mediated mechanisms. Infected individuals develop specific antibodies capable of neutralizing the ability of virus to enter certain cell types. These neutralizing antibodies to the viral envelope can protect against reinfection with SARS‐CoV‐2. In addition, nonneutralizing antibodies to the viral surface proteins provide no protection against viral challenge and potentiate the uptake of virus particles by Fc receptor‐bearing cells including macrophages, monocytes, B cells, and endothelium cells leading to viral persistence. The so‐called enhancing antibodies have substantial effects through antibody Fc‐mediated effector function which amplify the overwhelming cytokine storm and, potentially, exacerbate disease pathologies. This phenomenon is called antibody‐dependent enhancement (ADE) of infection. The role of infectivity‐enhancing antibodies raises issues about the development of SARS‐CoV‐2 virus vaccines and the use of passive antibody therapy. This is perhaps an important challenge in SARS‐CoV‐2 vaccine research. The goal of the current vaccine research programs should be therefore to develop antibodies for the virus eradication. Ab, antibody; IgG, immunoglobulin G; SARS ‐CoV‐2, severe acute respiratory syndrome coronavirus 2