Molecular Approaches in COVID-19 Treatment


Güven M. , Batar B.

in: Coronavirus Disease: From Molecular to Clinical Perspectives, Yıldız Dinçer, Editor, NOVA Science Publishers Inc. , New York, pp.283-299, 2021

  • Publication Type: Book Chapter / Chapter Research Book
  • Publication Date: 2021
  • Publisher: NOVA Science Publishers Inc.
  • City: New York
  • Page Numbers: pp.283-299
  • Editors: Yıldız Dinçer, Editor

Abstract

Coronaviruses are a family of enveloped RNA viruses that cause diseases in various mammals and birds. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus identified as the cause of a global infectious disease called coronavirus disease 2019 (COVID-19). To date, there are currently no specific antiviral drugs that have been shown to effectively treat COVID-19. Moreover, vaccines based on viral-encoded peptides may not be effective against COVID-19, as virus mutations could make them futile. Many therapeutic strategies can be predicted in controlling and preventing the SARS-CoV-2 infections, such as oligonucleotide-based therapy, neutralizing monoclonal antibody therapy, autophagy pathway as therapeutic targets, chimeric antigen receptor T-cell (CAR-T) therapy, and mesenchymal-derived exosome therapy. Synthetic oligonucleotide-based therapeutic options containing small interfering RNA (siRNA) and antisense oligonucleotide (ASO) target the virus itself and mediate the silencing of its genome. Neutralizing monoclonal antibodies that target the receptor-binding motif (RBM) can prevent the virus from binding to angiotensin-converting enzyme 2 (ACE2), and are therefore promising antiviral drugs. On the other hand, vaccines and drugs can be developed to target the spike (S) glycoprotein of the coronavirus.

Autophagy plays an important role in viral infection. Autophagosomes can induce apoptotic cell death of virally infected cells and disrupt the virus replication cycle. CAR-T treatment is a successful therapeutic option for patients with relapsed and/or refractory hematologic malignancies. Increased interleukin-6 (IL-6) is related to cytokine storm syndrome (CSS) in COVID-19 patients. CAR-T therapy is used successfully in the blocking of IL-6. Therefore, IL-6 can be a specific target for CAR-T therapy in SARS-CoV-2 infected patients. Mesenchymal-derived exosomes demonstrate anti-inflammatory and immunomodulatory effects. MSC-derived exosomes can modulate the activity of T cells. MSC-derived exosomes may inhibit pro-inflammatory cytokines and increase the levels of anti-inflammatory cytokines such as IL-10 in SARS-CoV-2 infection. MSC-derived exosomes have been considered a specific therapeutic option for COVID-19 patients. Future preclinical and clinical investigations are needed to understand the critical roles of these therapy approaches in COVID-19.