Potential Therapeutic Options for COVID-19: Current Status, Challenges, and Future Perspectives

Abstract

The COVID-19 pandemic represents an unprecedented challenge for the researchers to offer safe, tolerable, and effective treatment strategies for its causative agent known as SARS-CoV-2. With the rapid evolution of the pandemic, even the off-label use of existing drugs has been restricted by limited availability. Several old antivirals, antimalarial, and biological drugs are being reconsidered as possible therapies. The effectiveness of the controversial treatment options for COVID-19 such as nonsteroidal antiinflammatory drugs, angiotensin 2 conversion enzyme inhibitors and selective angiotensin receptor blockers was also discussed. A systemic search in the PubMed, Science Direct, LitCovid, Chinese Clinical Trial Registry, and ClinicalTrials.gov data bases was conducted using the keywords "coronavirus drug therapy," passive immunotherapy for COVID-19', "convalescent plasma therapy," (CPT) "drugs for COVID-19 treatment," "SARS-CoV-2," "COVID-19," "2019-nCoV," "coronavirus immunology," "microbiology," "virology," and individual drug names. Systematic reviews, case presentations and very recent clinical guidelines were included. This narrative review summarizes the available information on possible therapies for COVID-19, providing recent data to health professionals.

Keywords: COVID-19 proposed therapy; Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); convalescent plasma; pandemic; therapeutic challenges.

Figure 1

Schematic representation of structure and RNA genome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). (A) Structure of SAR-CoV-2. (B) RNA genome sequence of SARS-CoV-2. 3CL^PRO, 3-Chymotrypsin-like protease; Hel, helicase; ORF1a/b, Open reading frame 1a/b; PL^PRO, Papain-like protease; RdRp, RNA-dependent RNA polymerase. At 5ʹ end 67% viral genome contains two open reading frames (ORF1a and ORF1b) that encode two significant replicase genes (rep1a and rep1b), and which helps to express large replicase polyprotein 1a/ab (pp1a and pp1ab) (Islam et al., 2020). These polyproteins produce nonstructural proteins (e.g., RNA-dependent RNA polymerase (RdRp) and helicase) after the cleavage with the help of two enzymes, papain-like cysteine protease (PL^PRO) and 3-chymotrypsin-like serine protease (3CL^PRO) (Zumla et al., 2016). At 3ʹ end 33% viral genome encodes the structural proteins (e.g., S, M, E, and N), which are required for the attachment of virus particle and entry of the viral genome into the host cell (Peiris et al., 2004).

Figure 2

Schematic representation of virus-based treatment responses by targeting the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) replication cycle and SARS-CoV-2 associated acute respiratory distress syndrome. The proposed targets of most important candidates are noted. ACE2R, angiotensin-converting enzyme 2 receptor; ARDS, acute respiratory distress syndrome; ER, endoplasmic reticulum; E, envelope protein; Ig, immunoglobulin; M, membrane protein; N, nucleocapsid protein; Nab, neutralizing antibody; RdRp, RNA-dependent RNA polymerase; S, spike glycoprotein; TMPRSS2, type 2 transmembrane serine protease.

Figure 3

Schematic represents convalescent plasma components and the viral neutralizing activity of convalescent plasma.

Figure 4

A comparative scheme regarding the imbalanced host response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection versus other common respiratory virus infections. ISGs, IFN-stimulated genes.