VV116, mindeudesivir, deuremidevir for COVID-19

Coronavirus, a large family of positive-sense RNA viruses, are responsible for both mild and severe respiratory illnesses, ranging from the common cold to life-threatening conditions. Despite significant advances in vaccine and antiviral development, the high mutability of human coronaviruses (HCoVs), such as SARS-CoV-2, presents a major challenge in treating these infections. Effective, broad-spectrum antiviral drugs are urgently needed to address both current and future HCoV outbreaks. Here, we conducted high-throughput screening of a natural product library containing 3407 compounds to identify potential antiviral agents against HCoV-OC43 and HCoV-229E. We identified several natural products with inhibitory effects on HCoV-229E, HCoV-OC43, and the SARS-CoV-2 variants Delta (B.1.617.2) and Omicron (BA.5) in vitro without evident cytotoxicity. Among these, dibenzoylmethane (DBM) not only demonstrated broad-spectrum anticoronavirus activity in vitro but also effectively inhibited HCoV-OC43 replication in a BALB/c mouse model. Pharmacokinetic analysis revealed that DBM, when administered orally, maintained effective concentrations in the blood over an extended period, suggesting its suitability for oral administration. Mechanistically, DBM was found to regulate caspase-6, a host factor that suppresses interferon signalling and promotes HCoV replication. These findings highlight DBM as a promising candidate for the development of therapeutics targeting HCoVs, offering potential for treating infections by both established and emerging HCoVs.

Since the onset of the COVID-19 pandemic, remarkable progress has been made in the development of antiviral therapies for SARS-CoV-2. Several direct-acting antivirals, such as remdesivir, molnupiravir, and nirmatrelvir/ritonavir, offer clinical benefits. These agents have significantly contributed to reducing the viral loads and duration of the illness, as well as the disease’s severity and mortality. However, despite these advances, important limitations remain. The continued emergence of resistant SARS-CoV-2 variants highlights the urgent need for adaptable and durable therapeutic strategies. Therefore, this review aims to provide an updated overview of the main antiviral strategies that are used and the discovery of new drugs against SARS-CoV-2, as well as the therapeutic limitations that have shaped clinical management in recent years. The major challenges include resistance associated with viral mutations, limited treatment windows, and unequal access to treatment. Moreover, there is an ongoing need to identify novel compounds with broad-spectrum activity, improved pharmacokinetics, and suitable safety profiles. Combination treatment regimens represent a promising strategy to increase the efficacy of treating COVID-19 while minimizing the potential for resistance. Ideally, these interventions should be safe, affordable, and easy to administer, which would ensure broad global access and equitable treatment and enable control of COVID-19 cases and preparedness for future threats.

Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant pneumonia in December 2019, the cumulative number of infected people worldwide has exceeded 670 million, with over 6.8 million deaths. Despite the marketing of multiple series of vaccines and the implementation of strict prevention and control measures in many countries, the spread and prevalence of SARS-CoV-2 have not been completely and effectively controlled. The latest research shows that in addition to angiotensin converting enzyme II (ACE2), dozens of protein molecules, including AXL, can act as host receptors for SARS-CoV-2 infecting human cells, and virus mutation and immune evasion never seem to stop. To sum up, this review summarizes and organizes the latest relevant literature, comprehensively reviews the genome characteristics of SARS-CoV-2 as well as receptor-based pathogenesis (including ACE2 and other new receptors), mutation and immune evasion, vaccine development and other aspects, and proposes a series of prevention and treatment opinions. It is expected to provide a theoretical basis for an in-depth understanding of the pathogenic mechanism of SARS-CoV-2 along with a research basis and new ideas for the diagnosis and classification, of COVID-19-related disease and for drug and vaccine research and development.

The novel coronavirus disease (COVID-19) continues to endanger human health, and its therapeutic drugs are under intensive research and development. Identifying the efficacy and toxicity of drugs in animal models is helpful for further screening of effective medications, which is also a prerequisite for drugs to enter clinical trials. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) invades host cells mainly by the S protein on its surface. After the SARS-CoV-2 RNA genome is injected into the cells, M protein will help assemble and release new viruses. RdRp is crucial for virus replication, assembly, and release of new virus particles. This review analyzes and discusses 26 anti-SARS-CoV-2 drugs based on their mechanism of action, effectiveness and safety in different animal models. We propose five drugs to be the most promising to enter the next stage of clinical trial research, thus providing a reference for future drug development.