Perspective on the Role of Antibodies and Potential Therapeutic Drugs to Combat COVID-19

Abstract

The sudden emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease of 2019 (COVID-19) has brought the world to a standstill. Thousands of people across the globe are biting the dust with every passing day and yet more are being tested positive for the SARS-CoV-2 infection. In order to dispense this current crisis, numerous treatment options have been tried and tested and many more are still under scrutiny. The development of vaccines may help in the prevention of the global pandemic, however, there is still a need for the development of alternate approaches to combat the disease. In this review we highlight the new discoveries and furtherance in the antibody based therapeutic options and the potent drugs, with special emphasis on the development of the monoclonal and polyclonal antibodies and the repurposed drugs, which may prove to be of significant importance for the treatment of COVID-19, in the days to come. It is an attempt to evaluate the currently presented challenges so as to provide a scope for the ongoing research and assistance in the development of the effective therapeutic options against SARS-CoV-2.

Keywords: Antibody; COVID-19; Convalescent plasma; Cytokine; SARS-CoV-2; Therapeutic drug.

Fig. 1

Inhibitory functions and roles of different antibodies and re-purposed drugs for battling COVID-19. The COVID-19 (coronavirus disease of 2019) infection begins with the attachment of the spike protein of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) to the ACE2 (angiotensin converting enzyme 2) human receptor. Various monoclonal (mAb) and polyclonal antibodies are being designed and convalescent plasma collected from the donor patients are being used to inhibit the attachment of the novel virus. This is followed by the virus and host membrane fusion and entry of the virus which is inhibited by drugs like Hydroxychloroquine (HCQ) and Chloroquine (CQ). Once the uncoating occurs and the viral RNA is released, it starts replicating with the help of the enzyme RNA dependent RNA polymerase (RdRp). Drugs like Remdesivir, Favipiravir and Ribavirin, interfere with the activity of this enzyme. In order to further generate viral proteins, the processing (capping) of the viral RNA is required for maintaining its stability. This processing is inhibited by drugs like Ribavirin. On the other hand, combination of Lopinavir and Ritonavir is used for inhibiting the proteases like 3CL^pro (chymotrypsin like cysteine protease) which are mainly responsible for the proteolytic cleavage and generation of non-structural proteins involved in viral replication. Once the viral assembly is complete and the new virions are ready, the exocytosis of these virions occur. This is inhibited by drugs like CQ and HCQ. The infection by the novel virus and release of the new virions which infect the neighbouring cells of the body lead to an exaggerated cytokine release which can be managed using drugs like corticosteroids, various mAbs targeting different cytokines and cytokine receptors, etc.