Therapeutic modalities and novel approaches in regenerative medicine for COVID-19

Abstract

The recent coronavirus disease 2019 outbreak around the world has had an enormous impact on the global health burden, threatening the lives of many individuals, and has had severe socio-economic consequences. Many pharmaceutical and biotechnology companies have commenced intensive research on different therapeutic strategies, from repurposed antiviral drugs to vaccines and monoclonal antibodies to prevent the spread of the disease and treat infected patients. Among the various strategies, advanced therapeutic approaches including cell- and gene-editing-based therapeutics are also being investigated, and initial results in in-vitro and early phase I studies have been promising. However, further assessments are required. This article reviews the underlying mechanisms for the pathogenesis of severe acute respiratory syndrome coronavirus-2, and discusses available therapeutic candidates and advanced modalities that are being evaluated in in-vitro/in-vivo models and are of note in clinical trials.

Keywords: ATMP; Advanced therapeutic approaches; COVID-19; SARS-CoV-2.

Fig. 1

Overview of the structure of severe acute respiratory syndrome coronavirus-2. ssRNA, single-strand RNA.

Fig. 2

Pathogenesis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). (A) Fever, cough and headache are common symptoms of coronavirus disease 2019. Acute respiratory distress syndrome and multi-organ failure account for the critical stage of the disease (left). Type II alveolar cells highly express angiotensin-converting enzyme-2 (ACE2), the receptor for SARS-CoV-2 (right). (B) Virus entry mechanism and enzymes involved in this process. APC, antigen-presenting cell (created using Biorender,com).

Fig. 3

(A) Viral genome replication and subgenomic mRNA (sgmRNA) synthesis. (B) Interaction of antigen-presenting cells (APCs) with lymphocytes and cytokine activation (created using Biorender.com). ARDS, acute respiratory distress syndrome; IFN, interferon; IL, interleukin; TCR, T-cell receptor; MHC, major histocompatibility complex; PP1a, polyprotein 1a; PP1ab, polyprotein 1ab.

Fig. 4

Therapeutics. (A) Current therapeutics used to treat patients with coronavirus disease 2019. (B) Advanced therapeutic medicinal products (ATMPs), with cell- and gene-based candidate therapies (created by Biorender.com). mAbs, monoclonal antibodies; DC, dendritic cell; aAPC, artificial antigen-presenting cell; NK, natural killer; SCE, stem cell educator; MSC, mesenchymal stem/stromal cell.