Anti-coronavirus Agents Research Articles

Synthesis and evaluation of N-arylindazole-3-carboxamide derivatives as novel antiviral agents against SARS-CoV-2

N-Arylindazole-3-carboxamide derivatives synthesized from an anti-MERS-CoV hit compound showed potent inhibitory activities against SARS-CoV-2. Among them, 5-chloro-N-(3,5-dichlorophenyl)-1H-indazole-3-carboxamide (4a) exhibited a potent inhibitory effect (EC50 = 0.69 µM), low cytotoxicity, and satisfactory in vitro PK profiles. Thus, N-arylindazole-3-carboxamide 4a provides a novel template for future development of anti-coronavirus agents.

Molecular Modeling Studies of Similar Molecules to Selective Estrogen Receptor Degrader Elacestrant as Inhibitors of SARS-COV-2.

Coronavirus 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) strain. Many anticancer compounds have been repurposed as effective anti-coronavirus agents and are currently in a clinical trial to be evaluated for treatment. Elacestrant is a novel selective estrogen receptor degrader (SERD). A fingerprint Tanimoto-based 2-dimensional similarity search was performed in the PubChem database using elacestrant as a prototype. The chemical compounds were downloaded, and virtual screening, molecular docking, and molecular dynamics were further used to identify the most active molecules in the binding pocket SARS-COV-2 main protease. Eight compounds with superior docking score, gscore, and glide binding energy were identified. Molecular dynamic simulations (MD) were performed at 100 ns to remove the false interactions between the receptor and the active ligands. The results showed that all the compounds displayed good stability. Further, the ADMET results showed that compounds CID58023104 was observed to be deemed a hit compound; hence, CID58023104 and could be optimize, derivatize, and explore for further development as an anti-coronavirus agent targeting SARS-COV-2 main protease.

NanoLuciferase technology-based detection of TMPRSS2 as attempt to develop anti-coronavirus agents

•Utilized NanoBiT technology for high-throughput screening.•Identified compounds reducing TMPRSS2 expression, a crucial step for SARS-CoV-2 entry.•Explored a broad range of compound libraries.

Inhibitors of SARS-CoV-2 Main Protease (Mpro) as Anti-Coronavirus Agents.

The main protease (Mpro) of SARS-CoV-2 is an essential enzyme that plays a critical part in the virus's life cycle, making it a significant target for developing antiviral drugs. The inhibition of SARS-CoV-2 Mpro has emerged as a promising approach for developing therapeutic agents to treat COVID-19. This review explores the structure of the Mpro protein and analyzes the progress made in understanding protein-ligand interactions of Mpro inhibitors. It focuses on binding kinetics, origin, and the chemical structure of these inhibitors. The review provides an in-depth analysis of recent clinical trials involving covalent and non-covalent inhibitors and emerging dual inhibitors targeting SARS-CoV-2 Mpro. By integrating findings from the literature and ongoing clinical trials, this review captures the current state of research into Mpro inhibitors, offering a comprehensive understanding of challenges and directions in their future development as anti-coronavirus agents. This information provides new insights and inspiration for medicinal chemists, paving the way for developing more effective Mpro inhibitors as novel COVID-19 therapies.

Discovery of C-Linked Nucleoside Analogues with Antiviral Activity against SARS-CoV-2.

The recent COVID-19 pandemic underscored the limitations of currently available direct-acting antiviral treatments against acute respiratory RNA-viral infections and stimulated major research initiatives targeting anticoronavirus agents. Two novel nsp5 protease (MPro) inhibitors have been approved, nirmatrelvir and ensitrelvir, along with two existing nucleos(t)ide analogues repurposed as nsp12 polymerase inhibitors, remdesivir and molnupiravir, but a need still exists for therapies with improved potency and systemic exposure with oral dosing, better metabolic stability, and reduced resistance and toxicity risks. Herein, we summarize our research toward identifying nsp12 inhibitors that led to nucleoside analogues 10e and 10n, which showed favorable pan-coronavirus activity in cell-infection screens, were metabolized to active triphosphate nucleotides in cell-incubation studies, and demonstrated target (nsp12) engagement in biochemical assays.

Insights into the Dynamics and Binding of Two Polyprotein Substrate Cleavage Points in the Context of the SARS-CoV-2 Main and Papain-like Proteases.

It is well known that vital enzymes in the replication process of the coronavirus are the SARS-CoV-2 PLpro and SARS-CoV-2 3CLpro, both of which are important targets in the search for anti-coronavirus agents. These two enzymes are responsible for cleavage at various polyprotein sites in the SARS-CoV-2 lifecycle. Herein, the dynamics of the polyprotein cleavage sequences for the boundary between non-structural proteins Nsp1 and Nsp2 (CS1) and between Nsp2 and Nsp3 (CS2) in complex with both the papain-like protein PLpro and the main protease 3CLpro were explored using computational methods. The post dynamics analysis reveals that CS1 and CS2 both have greater stability when complexed with PLpro. Of these two, greater stability is observed for the CS1-PLpro complex, while destabilization resulting in loss of CS2 from the PLpro active site is observed for CS2-PLpro, suggesting the rate of exchange by the papain-like protease is faster for CS2 compared to CS1. On the other hand, the 3CLpro main protease also reveals stability for CS1 suggesting that the main protease could also play a potential role in the cleavage at point CS1. However, destabilization occurs early in the simulation for the complex CLpro-CS2 suggesting a poor interaction and non-plausible protease cleavage of the polyprotein at CS2 by the main protease. These findings could be used as a guide in the development and design of potent COVID-19 antiviral inhibitors that mimic the CS1 cleavage site.

Allosteric Binding Sites of the SARS-CoV-2 Main Protease: Potential Targets for Broad-Spectrum Anti-Coronavirus Agents.

The current pandemic caused by the COVID-19 disease has reached everywhere in the world and has affected every aspect of our lives. As of the current data, the World Health Organization (WHO) has reported more than 300 million confirmed COVID-19 cases worldwide and more than 5 million deaths. Mpro is an enzyme that plays a key role in the life cycle of the SARS-CoV-2 virus, and it is vital for the disease progression. The Mpro enzyme seems to have several allosteric sites that can hinder the enzyme catalytic activity. Furthermore, some of these allosteric sites are located at or nearby the dimerization interface which is essential for the overall Mpro activity. In this review paper, we investigate the potential of the Mpro allosteric site to act as a drug target, especially since they interestingly appear to be resistant to mutation. The work is illustrated through three subsequent sections: First, the two main categories of Mpro allosteric sites have been explained and discussed. Second, a total of six pockets have been studied and evaluated for their druggability and cavity characteristics. Third, the experimental and computational attempts for the discovery of new allosteric inhibitors have been illustrated and discussed. To sum up, this review paper gives a detailed insight into the feasibility of developing new Mpro inhibitors to act as a potential treatment for the COVID-19 disease.

Are Plant-derived Flavonoids the Emerging Anti-coronavirus Agents?

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Are Plant-derived Flavonoids the Emerging Anti-coronavirus Agents?

The current outbreak of coronavirus disease 2019 (COVID-19), which is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has negatively impacted the global health and economy. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shares many similarities with SARS-CoV and Middle East respiratory syndrome-related coronavirus. It has been identified that the 3C-like protease (3CLpro) enzyme in coronaviruses can be a major therapeutic target for combating these serious infections. Therefore, flavonoids are believed to hold high potential in eliminating the viruses and infections. Flavonoids are polyphenolic secondary metabolites found in plants and have been demonstrated for their notable benefits for health. The antiviral activity of flavonoids has been reported in recent studies. Flavonoids, such as apigenin, quercetin, luteolin, amentoflavone, epigallocatechin gallate, gallocatechin gallate, and kaempferol, are known to be able to fight against coronaviruses by reducing the 3CLpro activity, according to the docking studies. Besides, we also found that several flavonoids have the potential to suppress the inflammatory cytokines, which are generally expressed in the lungs of coronavirus-infected individuals. However, the studies utilizing 3CLpro using various scaffolds of flavonoids need to be performed for better understanding on the antiviral potential of flavonoid derivatives against 3CLpro.

Targeting papain-like protease for broad-spectrum coronavirus inhibition

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.

Mechanism of Antiviral Activities of Nanoviricide's Platform Technology based Biopolymer (NV-CoV-2).

NV-CoV-2 is a nanoviricide that is covalently bonded with polyethylene glycol (PEG) and alkyl pendants. This molecular design is used to attack many strains of coronaviruses in a broad-spectrum manner. The ligand works by competitive inhibition and binds to the same site on the S-protein of SARS-CoV that attaches to the cognate cellular receptor, ACE2. This prevents SARS-CoV from binding and infecting the cell. NV-CoV-2 is designed to bind to the free virion particles at multiple points encapsulate the virus and disable its ability to infect the cells. The multi-point binding interaction, like a nano-velcro-tape, may lead to lipid-lipid fusion of the alkyl chains in the nanoviricide micelle with the lipid envelope of the virus. The virus becomes dismantled to a capsid form before the host immune system becomes involved. This putative mechanism is orthogonal to many other anti-coronavirus agents in development. Thus, it maybe possible to produce a stronger antiviral effect when combining NV-CoV-2 therapy with other anti-coronavirus therapies such as Remdesivir (RDV). NV-CoV-2 can encapsulate other antiviral compounds as well. In this study, RDV was encapsulated and protected from serum-mediated degradation in vivo. As a result, RDV was available for a longer period of time to interact with RNA polymerase and inhibit.

The role of medicinal plants in the treatment of Coronavirus infections

The coronavirus family consists of numerous species that cause respiratory and gastrointestinal infections in vertebrates, but some members such as SARS, MERS, and SARS-CoV-2 are particularly dangerous to humans. So far, SARS-CoV-2 is confirmed in 636.440.663 patients worldwide, and it is responsible for 6.606.624 deaths. Plants possess a number of chemical constituents, which act as inhibitors of viral proteins and can be used in the treatment of viral diseases, with a lower rate of virus resistance. The retrospective investigation covered a period of 27 years, from 1995 to 2022 and it is implemented through the analysis of results from previously reported studies focused on alternative anti-coronavirus agents. The total of 73 plant species from 46 families, with reported anti-coronavirus activity, was noted. Considering the number of species with anti-coronavirus effects, the most prevalent family was Fabaceae with 9.59%. Many bioactive compounds were secondary metabolites, and the vast majority was isolated from leaves. The anti-coronavirus activity of plant products was recorded against six coronaviruses: SARS-CoV, SARS-CoV-2, MERS-CoV, BCV, HCoV-OC43, and HCoV-NL63. Among the mechanisms of antiviral action, the inhibition of 3-chymotrypsin-like protease, 3Clpro was frequently described. This study illustrated the high potential of plants and their products in terms of anti-coronaviral compounds. Since viruses represent molecular pathogens, with high mutations range as well as resistance to synthetic antiviral drugs, a novel investigation should be oriented towards the isolation and characterization of efficient antiviral agents of natural origin.

Structure-Based Discovery and Structural Basis of a Novel Broad-Spectrum Natural Product against the Main Protease of Coronavirus.

ABSTRACTOver the past 20 years, the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and SARS-CoV-2 emerged, causing severe human respiratory diseases throughout the globe. Developing broad-spectrum drugs would be invaluable in responding to new, emerging coronaviruses and to address unmet urgent clinical needs. Main protease (Mpro; also known as 3CLpro) has a major role in the coronavirus life cycle and is one of the most important targets for anti-coronavirus agents. We show that a natural product, noncovalent inhibitor, shikonin, is a pan-main protease inhibitor of SARS-CoV-2, SARS-CoV, MERS-CoV, human coronavirus (HCoV)-HKU1, HCoV-NL63, and HCoV-229E with micromolar half maximal inhibitory concentration (IC50) values. Structures of the main protease of different coronavirus genus, SARS-CoV from the betacoronavirus genus and HCoV-NL63 from the alphacoronavirus genus, were determined by X-ray crystallography and revealed that the inhibitor interacts with key active site residues in a unique mode. The structure of the main protease inhibitor complex presents an opportunity to discover a novel series of broad-spectrum inhibitors. These data provide substantial evidence that shikonin and its derivatives may be effective against most coronaviruses as well as emerging coronaviruses of the future. Given the importance of the main protease for coronavirus therapeutic indication, insights from these studies should accelerate the development and design of safer and more effective antiviral agents.IMPORTANCE The current pandemic has created an urgent need for broad-spectrum inhibitors of SARS-CoV-2. The main protease is relatively conservative compared to the spike protein and, thus, is one of the most promising targets in developing anti-coronavirus agents. We solved the crystal structures of the main protease of SARS-CoV and HCoV-NL63 that bound to shikonin. The structures provide important insights, have broad implications for understanding the structural basis underlying enzyme activity, and can facilitate rational design of broad-spectrum anti-coronavirus ligands as new therapeutic agents.

Natural Products as Potential Agents against SARS-CoV and SARSCoV- 2.

Natural products are useful agents for the discovery of new lead- compounds and effective drugs to combat coronaviruses (CoV). The present work provides an overview of natural substances, plant extracts, and essential oils as potential anti-SARS-CoV agents. In addition, this work evaluates their drug-like properties which are essential in the selection of compounds in order to accelerate the drug development process. The search was carried out using PubMed, ScienceDirect and SciFinder. Articles addressing plant-based natural products as potential SARS-CoV or SARS-CoV-2 agents within the last seventeen years were analyzed and selected. The descriptors for Chemometrics analysis were obtained in alvaDesc and the principal component analysis (PCA) was carried out in SIMCA version 13.0. Based on in vitro assays and computational analyses, this review covers twentynine medicinal plant species and more than 300 isolated substances as potential anti-coronavirus agents. Among them, flavonoids and terpenes are the most promising compound classes. In silico analyses of drug-like properties corroborate these findings and indicate promising candidates for in vitro and in vivo studies to validate their activity. This paper highlights the role of ethnopharmacology in drug discovery and suggests the use of integrative (in silico/ in vitro) and chemocentric approaches to strengthen current studies and guide future research in the field of antiviral agents.

Potential Anti-Coronavirus Agents and the Pharmacologic Mechanisms.

Severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) is an emerging pathogen, which is similar to previous SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) occurrences. However, we only get few understandings about the pathogenesis of SARS-CoV-2, which need to further be studied. The discovery of an agent that has a treatment efficacy against SARS-CoV-2 is very urgent. In this review, we briefly discuss the virology of this pathogen and focus on the available understanding of the pathogenesis and treatments of this pathogen including the uses of nucleoside analogues, protease inhibitors, interferons, and other small-molecule drugs, on the basis previous comprehensions of SARS and MERS. These reviewed concepts may be beneficial in providing new insights and potential treatments for COVID-19.

HBD-2 Binds SARS-CoV-2 RBD and Blocks Viral Entry: Strategy to Combat COVID-19

New approaches to complement vaccination are needed to combat the spread of SARS-CoV-2 and stop COVID-19 related deaths and medical complications. Human beta defensin 2 (hBD-2) is a naturally occurring epithelial cell derived host defense peptide that has antiviral properties. Our comprehensive in-silico studies demonstrate that hBD-2 binds the site on the CoV-2-RBD that docks with the ACE2 receptor. Biophysical and biochemical assays confirm that hBD-2 indeed binds to the CoV-2-receptor binding domain (RBD) (KD ~ 300 nM), preventing it from binding to ACE2 expressing cells. Importantly, hBD-2 shows specificity by blocking CoV-2/spike pseudoviral infection, but not VSV-G mediated infection, of ACE2 expressing human cells with an IC50 of 2.4± 0.1 μM. These promising findings offer opportunities to develop hBD-2 and/or its derivatives and mimetics to safely and effectively use as novel agents to prevent SARS-CoV-2 infection.Funding Statement: LZ: Energy Center of TTU helped support JP; pilot funds from Drs. Weinberg and Buck for undergraduate student Ann Brewer. PR: We thank Dr. Jesse Bloom, Fred Hutchinson Cancer Center for kindly proving the plasmids to generate Spike pseudovirus and ACE2 expressing HEK 293T cells. PR funded by NIH/NIAID R01AI116730, R21AI144264, NIH/NCI grant R21 CA246194 and pilot funding from NORD Family Foundation. MB: Thanks to Dr. Parvesh Shrestha for help with MST experiments. MB funded by NIH/NEI R01EY029169 and by a pilot grant from the Department of Physiology and Biophysics of CWRU. AW: Studies herein supported by NIH/NCI R21CA253108, NIH/NIDCR R21DE028416 and pilot funds from the Department of Biological Sciences of the School of Dental Medicine, CWRU.Declaration of Interests: LZ, SKG, PR, MB and AW are co-inventors in using AMPs, and their derivatives, as anti-coronavirus agents, and have submitted an invention disclosure to Case Western Reserve University. S.C.B. J.M-G, J.P. and A.B. declare no competing interests.

Nucleotide analogues as inhibitors of SARS-CoV Polymerase.

SARS‐CoV‐2, a member of the coronavirus family, has caused a global public health emergency. Based on our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously reasoned that the FDA‐approved hepatitis C drug EPCLUSA (Sofosbuvir/Velpatasvir) should inhibit coronaviruses, including SARS‐CoV‐2. Here, using model polymerase extension experiments, we demonstrate that the active triphosphate form of Sofosbuvir is incorporated by low‐fidelity polymerases and SARS‐CoV RNA‐dependent RNA polymerase (RdRp), and blocks further incorporation by these polymerases; the active triphosphate form of Sofosbuvir is not incorporated by a host‐like high‐fidelity DNA polymerase. Using the same molecular insight, we selected 3’‐fluoro‐3’‐deoxythymidine triphosphate and 3’‐azido‐3’‐deoxythymidine triphosphate, which are the active forms of two other anti‐viral agents, Alovudine and AZT (an FDA‐approved HIV/AIDS drug) for evaluation as inhibitors of SARS‐CoV RdRp. We demonstrate the ability of two of these HIV reverse transcriptase inhibitors to be incorporated by SARS‐CoV RdRp where they also terminate further polymerase extension. Given the 98% amino acid similarity of the SARS‐CoV and SARS‐CoV‐2 RdRps, we expect these nucleotide analogues would also inhibit the SARS‐CoV‐2 polymerase. These results offer guidance to further modify these nucleotide analogues to generate more potent broad‐spectrum anti‐coronavirus agents.

Course and treatment of diabetes mellitus in the context of COVID-19

In 2020, the world is facing a historically unparalleled public health challenge associated with the invasion of the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This is also a challenge for the healthcare systems worldwide. Patients with diabetes mellitus (DM) are most vulnerable to COVID-19 because of the peculiarities of their immune response to a virus attack and due to their high susceptibility to viral activity because of hyperglycemia and other comorbid conditions and obesity that often accompany DM. The severity of the COVID-19 disease requires a mandatory review of the usual anti-hyperglycemic therapy. Maintaining optimal glycemic control and preventing the development of ketoacidosis remain extremely important; therefore, insulin becomes the priority drug for glycemic control in most cases. The search for new drugs to fight against the coronavirus infection continues with new randomised clinical drug trials being launched. Innovative anti-diabetic agents are also being tested as candidates for potentially effective anti-coronavirus agents.

Сахарный диабет в условиях вирусной пандемии COVID-19: особенности течения и лечения

In 2020, the world is facing a historically unparalleled public health challenge associated with the invasion of the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This is also a challenge for the healthcare systems worldwide. Patients with diabetes mellitus (DM) are most vulnerable to COVID-19 because of the peculiarities of their immune response to a virus attack and due to their high susceptibility to viral activity because of hyperglycemia and other comorbid conditions and obesity that often accompany DM. The severity of the COVID-19 disease requires a mandatory review of the usual anti-hyperglycemic therapy. Maintaining optimal glycemic control and preventing the development of ketoacidosis remain extremely important; therefore, insulin becomes the priority drug for glycemic control in most cases. The search for new drugs to fight against the coronavirus infection continues with new randomised clinical drug trials being launched. Innovative anti-diabetic agents are also being tested as candidates for potentially effective anti-coronavirus agents.

Recent research for COVID-19 drugs and therapies

<p indent="0mm">The sudden outbreak of COVID-19 is causing a severe health crisis to China and the world. The rapid spread coronavirus worldwide highlights the urgent need to find effective drugs and therapies to fight the COVID-19 and related diseases such as acute respiratory disease. Based on the current knowledge on the structure, pathogenic mechanism and pharmacy of coronavirus and previous understanding and experience in treating similar diseases, researchers are testing and screening the approved broad-spectrum antiviral drugs and compounds, and investigating new specific drugs aiming at curing COVID-19. Facing the coronavirus pandemic, it is essential methods and strategies to review existing broad-spectrum antiviral drugs and screen possible effective medicines through some compounds database or repository of structured medical information. Till now, scientists have proposed hundreds of possible drug candidates in a short period of time. This article summarized the potential drugs and treatments proposed by scientists, pharmaceutical industries, and clinicians through literature survey on PubMed—a medical academic database, two clinical trials databases, and internet information published before February 16th, 2020. Then a system review and analysis on the development situations and trends about COVID-19 drugs and therapies were carried out. According to the documents published, scientists and doctors have focused on several possible categories of drugs, including: (1) Chemical compounds, such as nucleoside analogues, protease inhibitors, and other antiviral drugs with multiple mechanisms; (2) biologics, such as monoclonal antibodies, interferon, peptides, plasma of recovered patients and some new kinds of therapies; (3) traditional Chinese medicines, such as some syndrome differentiation therapies. Now, nearly 100 agents or therapies have entered into the clinic research processes and some of them have arrived at the IV phase of clinical trials. Due to the considerable previous experiences and understands that have been accumulated in the researches on SARS-nCoV, Ebola, MERS, and AIDS, with the help of advanced biotechnology and medical technology, scientists can respond faster than ever before, and have investigated a variety of potential treatment options. For example, Remdesivir, which was originally targeted at Ebola virus, Kaletra, which has been used for the treatment of AIDS, Chloroquine, a typical drug used as antimalarial long time ago, glucocorticoids, a common therapies method used to combat SARS, washed microbiota transplantation and Mesenchymal Stem Cell, emerging biological therapies, and combination of multiple drugs or combination of traditional Chinese medicines and modern medicines, are bringing hope to treat COVID-19. Now scientists have proposed several drug candidates (e.g., Remdesivir, Kaletra, Arbidol and Chloroquine) that could be the potential anti-coronavirus agents. All of these drugs are under study in the late phases of clinical trials. While Remdesivir and Kaletra have already shown positive effect on COVID-19 related disease at personalized level. Traditional Chinese Medicines treatment with syndrome differentiation combined with modern medicines also shows a good effect. A considerable number of candidate drugs have shown good results<italic> in vitro</italic> cell tests on COVID-19. Currently, the follow-up animal tests, toxicology tests, and human clinical trials are in progress at various stages. After a period of clinical application research and further validation research on the clinical effect, safety, dosage and indications of these candidate drugs, it is expected that more drugs with significant efficacy will emerge. Finally, we will defeat COVID-19, and the public will live in a healthy and peaceful world.