Pharmacological therapies and drug development targeting SARS-CoV-2 infection.

The development of therapies for SARS-CoV-2 infection, based on virus biology and pathology, and of large- and small-scale randomized controlled trials, have brought forward several antiviral and immunomodulatory drugs targeting the disease severity. Casirivimab/Imdevimab monoclonal antibodies and convalescent plasma to prevent virus entry, Remdesivir, Molnupiravir, and Paxlovid nucleotide analogs to prevent viral replication, a variety of repurposed JAK-STAT signaling pathway inhibitors, corticosteroids, and recombinant agonists/antagonists of cytokine and interferons have been found to provide clinical benefits in terms of mortality and hospitalization. However, current treatment options face multiple clinical needs, and therefore, in this review, we provide an update on the challenges of the existing therapeutics and highlight drug development strategies for COVID-19 therapy, based on ongoing clinical trials, meta-analyses, and clinical case reports.

Cytokine storm in COVID-19: from viral infection to immune responses, diagnosis and therapy.

The COVID-19 outbreak is emerging as a significant public health challenge. Excessive production of proinflammatory cytokines, also known as cytokine storm, is a severe clinical syndrome known to develop as a complication of infectious or inflammatory diseases. Clinical evidence suggests that the occurrence of cytokine storm in severe acute respiratory syndrome secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is closely associated with the rapid deterioration and high mortality of severe cases. In this review, we aim to summarize the mechanism of SARS-CoV-2 infection and the subsequent immunological events related to excessive cytokine production and inflammatory responses associated with ACE2-AngII signaling. An overview of the diagnosis and an update on current therapeutic regimens and vaccinations is also provided.

Recent insights into COVID-19 through study of SARS and MERS

The outbreak of pneumonia caused by infection with a new type of coronavirus called "severe acute respiratory syndrome coronavirus 2" (SARS-Cov-2), in Wuhan, China, has morphed into a pandemic. By referring to existing studies on coronaviruses, the infection mechanism and source of SARS-CoV-2 has been clarified gradually. Investigation of the diagnosis and treatment of pneumonia caused by SARS-CoV-2 (which was named "coronavirus disease 2019" (COVID-19) by the World Health Organization on 11 February 2020) has been carried out. Through study of the infective process and receptors, various antiviral drugs have aroused our interest. Based on the emergence of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus in the 20005, and SARS-Cov-2, we discuss the development and evolution of coronaviruses, their source and route of transmission, infection and replication, preventive measures, diagnosis and potential treatment.

Antibody-dependent enhancement of coronavirus.

Antibody-dependent enhancement (ADE) exists in several kinds of virus. It has a negative influence on antibody therapy for viral infection. This effect was first identified in dengue virus and has since also been described for coronavirus. To date, the rapid spread of the newly emerged coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has affected over 3.8 million people across the globe. The novel coronavirus poses a great challenge and has caused a wave of panic. In this review, antibody-dependent enhancements in dengue virus and two kinds of coronavirus are summarized. Possible solutions for the effects are reported. We also speculate that ADE may exist in SARS-CoV-2.

Characteristics of the Coronavirus Disease 2019 and related Therapeutic Options.

The coronavirus disease 2019 (COVID-19) is a new type of pneumonia caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. COVID-19 is affecting millions of patients, and the infected number keeps increasing. SARS-CoV-2 is highly infectious, has a long incubation period, and causes a relatively high death rate, resulting in severe health problems all over the world. Currently there is no effective proven drug for the treatment of COVID-19; therefore, development of effective therapeutic drugs to suppress SARS-CoV-2 infection is urgently needed. In this review, we first summarize the structure and genome features of SARS-CoV-2 and introduce its infection and replication process. Then, we review the clinical symptoms, diagnosis, and treatment options of COVID-19 patients. We further discuss the potential molecular targets and drug development strategies for treatment of the emerging COVID-19. Finally, we summarize clinical trials of some potential therapeutic drugs and the results of vaccine development. This review provides some insights for the treatment of COVID-19.

In silico design of antiviral peptides targeting the spike protein of SARS-CoV-2.

An outbreak caused by 2019 novel coronavirus (2019-nCoV) was first identified in Wuhan City, Hubei Province, China. The new virus was later named SARS-CoV-2. The virus has affected tens of thousands of patients in the world. The infection of SARS-CoV-2 causes severe pneumonia and even death. It is urgently needed to find a therapeutic method to treat patients with SARS-CoV-2 infection. Studies showed that the surface spike (S) protein is essential for the coronavirus binding and entry of host cells. The heptad repeats 1 and 2 (HR1 and HR2) in the S protein play a decisive role in the fusion of the viral membrane with the host cell membrane. We predicted the HR1 and HR2 regions in S protein by sequence alignment. We simulated a computational model of HR1/2 regions and the fusion core. The binding energy of HR1 and HR2 of the fusion core was -33.4 kcal/mol. We then designed antivirus peptides by molecular dynamics simulation of the fusion core. The binding energy of HR2-based antiviral peptide to HR1 was -43.0 kcal/mol, which was stronger than the natural stage of the fusion core, suggesting that the predicted antiviral peptide can competitively bind with HR1 to prevent forming of the fusion core. The antiviral peptides can prevent SARS-CoV-2 membrane fusion and can potentially be used for the prevention and treatment of infections.