Current treatment strategies for COVID‑19 (Review)

Abstract

The spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) emerged suddenly at the end of 2019 and the disease came to be known as coronavirus disease 2019 (COVID‑19). To date, there is no specific therapy established to treat COVID‑19. Identifying effective treatments is urgently required to treat patients and stop the transmission of SARS‑CoV‑2 in humans. For the present review, >100 publications on therapeutic agents for COVID‑19, including in vitro and in vivo animal studies, case reports, retrospective analyses and meta‑analyses were retrieved from PubMed and analyzed, and promising therapeutic agents that may be used to combat SARS‑CoV‑2 infection were highlighted. Since the outbreak of COVID‑19, different drugs have been repurposed for its treatment. Existing drugs, including chloroquine (CQ), its derivative hydroxychloroquine (HCQ), remdesivir and nucleoside analogues, monoclonal antibodies, convalescent plasma, Chinese herbal medicine and natural compounds for treating COVID‑19 evaluated in experimental and clinical studies were discussed. Although early clinical studies suggested that CQ/HCQ produces antiviral action, later research indicated certain controversy regarding their use for treating COVID‑19. The molecular mechanisms of these therapeutic agents against SARS‑CoV2 have been investigated, including inhibition of viral interactions with angiotensin‑converting enzyme 2 receptors in human cells, viral RNA‑dependent RNA polymerase, RNA replication and the packaging of viral particles. Potent therapeutic options were reviewed and future challenges to accelerate the development of novel therapeutic agents to treat and prevent COVID‑19 were acknowledged.

Keywords: Chinese herbal medicine; RNA‑dependent RNA polymerase; antibodies; coronavirus disease 2019; nucleoside analogues; severe acute respiratory syndrome coronavirus 2.

Figure 1.

Genomic structure and potential drug targets for SARS-Cov-2, SARS-CoV and MERS-CoV. (A-C) Genomic organization of (A) SARS-Cov-2 (GenBank ID, MN908947.3), (B) SARS-CoV and (C) MERS-CoV, indicating the coding regions for proteins that are potential drug targets. (D) The main structural proteins of SARS-Cov-2 were indicated on viral particles. SARS-CoV, severe acute respiratory syndrome coronavirus; MERS-CoV, Middle Eastern respiratory syndrome coronavirus; RdRp, RNA-dependent RNA polymerase; S, spike; M, membrane; N, nucleocapsid; E, envelope.

Figure 2.

Pathogenesis of SARS-CoV-2 infection and molecular targets of antiviral therapeutics. The SARS-CoV-2 virus uses its spike proteins to bind to ACE2 receptors to enter human cells. Its RNA is released into the cytoplasm and translated to non-structural proteins such as RNA-dependent RNA polymerase. The positive strand of viral RNA is replicated to produce the negative strand of viral RNA, which is then transcribed to multiple positive-strand subgenomic RNA. The viral structural proteins, including the spike, envelope, membrane and nucleocapsid proteins, are translated and inserted into the endoplasmic reticulum. The subgenomic RNAs then combine with structural proteins and are packaged into the virus, which enters the Golgi vesicle to form the mature virion. Finally, the virion-containing vesicle fuses with the membrane of the host's cell to release the virus particles. The molecular targets of the antiviral therapeutics are denoted in green (chloroquine), purple (remdesivir), orange (mAbs) and black (CHM). SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; mAb, monoclonal antibodies; CHM, Chinese herbal medicine; ACE, angiotensin-converting enzyme; gRNA, guide RNA.