Baicalein for COVID-19

The COVID-19 pandemic, instigated by the emergence of the novel coronavirus, SARS-CoV-2, created an incomparable global health crisis. Due to its highly virulent nature, identifying potential therapeutic agents against this lethal virus is crucial. PLpro is a key protein involved in viral polyprotein processing and immune system evasion, making it a prime target for the development of antiviral drugs to combat COVID-19. To expedite the search for potential therapeutic candidates, this review delved into computational studies. Recent investigations have harnessed computational methods to identify promising inhibitors targeting PLpro, aiming to suppress the viral activity. Molecular docking techniques were employed by researchers to explore the binding sites for antiviral drugs within the catalytic region of PLpro. The review elucidates the functional and structural properties of SARS-CoV-2 PLpro, underscoring its significance in viral pathogenicity and replication. Through comprehensive all-atom molecular dynamics (MD) simulations, the stability of drug–PLpro complexes was assessed, providing dynamic insights into their interactions. By evaluating binding energy estimates from MD simulations, stable drug–PLpro complexes with potential antiviral properties were identified. This review offers a comprehensive overview of the potential drug/lead candidates discovered thus far against PLpro using diverse in silico methodologies, encompassing drug repurposing, structure-based, and ligand-based virtual screenings. Additionally, the identified drugs are listed based on their chemical structures and meticulously examined according to various structural parameters, such as the estimated binding free energy (ΔG), types of intermolecular interactions, and structural stability of PLpro–ligand complexes, as determined from the outcomes of the MD simulations. Underscoring the pivotal role of targeting SARS-CoV-2 PLpro in the battle against COVID-19, this review establishes a robust foundation for identifying promising antiviral drug candidates by integrating molecular dynamics simulations, structural modeling, and computational insights. The continual imperative for the improvement of existing drugs and exploring novel compounds remains paramount in the global efforts to combat COVID-19. The evolution and management of COVID-19 hinge on the symbiotic relationship between computational insights and experimental validation, underscoring the interdisciplinary synergy crucial to this endeavor.

Blocking the interaction between the SARS-CoV-2 spike protein and the human angiotensin-converting enzyme II (hACE2) protein serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate the symptoms of severe COVID-19. However, the emergence of SARS-CoV-2 variants has complicated the process of developing broad-spectrum drugs. As such, the aim of this study was to explore the efficacy of TCM treatments against SARS-CoV-2 variants through targeting the interaction of the viral spike protein with the hACE2 receptor. Antiviral activity was systematically evaluated using a pseudovirus system. Scutellaria baicalensis (S. baicalensis) was found to be effective against SARS-CoV-2 infection, as it mediated the interaction between the viral spike protein and the hACE2 protein. Moreover, the active molecules of S. baicalensis were identified and analyzed. Baicalein and baicalin, a flavone and a flavone glycoside found in S. baicalensis, respectively, exhibited strong inhibitory activities targeting the viral spike protein and the hACE2 protein, respectively. Under optimized conditions, virus infection was inhibited by 98% via baicalein-treated pseudovirus and baicalin-treated hACE2. In summary, we identified the potential SARS-CoV-2 inhibitors from S. baicalensis that mediate the interaction between the Omicron spike protein and the hACE2 receptor. Future studies on the therapeutic application of baicalein and baicalin against SARS-CoV-2 variants are needed.

Abstract Background The recent outbreak of the Coronavirus pandemic resulted in a successful vaccination program launched by the World Health Organization. However, a large population is still unvaccinated, leading to the emergence of mutated strains like alpha, beta, delta, and B.1.1.529 (Omicron). Recent reports from the World Health Organization raised concerns about the Omicron variant, which emerged in South Africa during a surge in COVID-19 cases in November 2021. Vaccines are not proven completely effective or safe against Omicron, leading to clinical trials for combating infection by the mutated virus. The absence of suitable pharmaceuticals has led scientists and clinicians to search for alternative and supplementary therapies, including dietary patterns, to reduce the effect of mutated strains. Main body This review analyzed Coronavirus aetiology, epidemiology, and natural products for combating Omicron. Although the literature search did not include keywords related to in silico or computational research, in silico investigations were emphasized in this study. Molecular docking was implemented to compare the interaction between natural products and Chloroquine with the ACE2 receptor protein amino acid residues of Omicron. The global Omicron infection proceeding SARS-CoV-2 vaccination was also elucidated. The docking results suggest that DGCG may bind to the ACE2 receptor three times more effectively than standard chloroquine. Conclusion The emergence of the Omicron variant has highlighted the need for alternative therapies to reduce the impact of mutated strains. The current review suggests that natural products such as DGCG may be effective in binding to the ACE2 receptor and combating the Omicron variant, however, further research is required to validate the results of this study and explore the potential of natural products to mitigate COVID-19. Graphical abstract

AbstractCOVID‐19, which was first identified in 2019 in Wuhan, China, is a respiratory illness caused by a virus called severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Although some patients infected with COVID‐19 can remain asymptomatic, most experience a range of symptoms that can be mild to severe. Common symptoms include fever, cough, shortness of breath, fatigue, loss of taste or smell and muscle aches. In severe cases, complications can arise including pneumonia, acute respiratory distress syndrome, organ failure and even death, particularly in older adults or individuals with underlying health conditions. Treatments for COVID‐19 include remdesivir, which has been authorised for emergency use in some countries, and dexamethasone, a corticosteroid used to reduce inflammation in severe cases. Biological drugs including monoclonal antibodies, such as casirivimab and imdevimab, have also been authorised for emergency use in certain situations. While these treatments have improved the outcome for many patients, there is still an urgent need for new treatments. Medicinal plants have long served as a valuable source of new drug leads and may serve as a valuable resource in the development of COVID‐19 treatments due to their broad‐spectrum antiviral activity. To date, various medicinal plant extracts have been studied for their cellular and molecular interactions, with some demonstrating anti‐SARS‐CoV‐2 activity in vitro. This review explores the evaluation and potential therapeutic applications of these plants against SARS‐CoV‐2. This review summarises the latest evidence on the activity of different plant extracts and their isolated bioactive compounds against SARS‐CoV‐2, with a focus on the application of plant‐derived compounds in animal models and in human studies.

In December 2019, an outbreak of a respiratory disease called the coronavirus disease 2019 (COVID-19) caused by a new coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China. The SARS-CoV-2, an encapsulated positive-stranded RNA virus, spread worldwide with disastrous consequences for people’s health, economies, and quality of life. The disease has had far-reaching impacts on society, including economic disruption, school closures, and increased stress and anxiety. It has also highlighted disparities in healthcare access and outcomes, with marginalized communities disproportionately affected by the SARS-CoV-2. The symptoms of COVID-19 range from mild to severe. There is presently no effective cure. Nevertheless, significant progress has been made in developing COVID-19 vaccine for different therapeutic targets. For instance, scientists developed multifold vaccine candidates shortly after the COVID-19 outbreak after Pfizer and AstraZeneca discovered the initial COVID-19 vaccines. These vaccines reduce disease spread, severity, and mortality. The addition of rapid diagnostics to microscopy for COVID-19 diagnosis has proven crucial. Our review provides a thorough overview of the historical development of COVID-19 and molecular and biochemical characterization of the SARS-CoV-2. We highlight the potential contributions from insect and plant sources as anti-SARS-CoV-2 and present directions for future research.

COVID-19 patients can exhibit a wide range of clinical manifestations affecting various organs and systems. Neurological symptoms have been reported in COVID-19 patients, both during the acute phase of the illness and in cases of long-term COVID. Moderate symptoms include ageusia, anosmia, altered mental status, and cognitive impairment, and in more severe cases can manifest as ischemic cerebrovascular disease and encephalitis. In this narrative review, we delve into the reported neurological symptoms associated with COVID-19, as well as the underlying mechanisms contributing to them. These mechanisms include direct damage to neurons, inflammation, oxidative stress, and protein misfolding. We further investigate the potential of small molecules from natural products to offer neuroprotection in models of neurodegenerative diseases. Through our analysis, we discovered that flavonoids, alkaloids, terpenoids, and other natural compounds exhibit neuroprotective effects by modulating signaling pathways known to be impacted by COVID-19. Some of these compounds also directly target SARS-CoV-2 viral replication. Therefore, molecules of natural origin show promise as potential agents to prevent or mitigate nervous system damage in COVID-19 patients. Further research and the evaluation of different stages of the disease are warranted to explore their potential benefits.

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.

Despite the fact that coronavirus disease 2019 (COVID-19) treatment and management are now considerably regulated, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still one of the leading causes of death in 2022. The availability of COVID-19 vaccines, FDA-approved antivirals, and monoclonal antibodies in low-income countries still poses an issue to be addressed. Natural products, particularly traditional Chinese medicines (TCMs) and medicinal plant extracts (or their active component), have challenged the dominance of drug repurposing and synthetic compound libraries in COVID-19 therapeutics. Their abundant resources and excellent antiviral performance make natural products a relatively cheap and readily available alternative for COVID-19 therapeutics. Here, we deliberately review the anti-SARS-CoV-2 mechanisms of the natural products, their potency (pharmacological profiles), and application strategies for COVID-19 intervention. In light of their advantages, this review is intended to acknowledge the potential of natural products as COVID-19 therapeutic candidates.

In the present study, we investigated the antiviral activities of 17 flavonoids as natural products. These derivatives were evaluated for their in vitro antiviral activities against HIV and SARS-CoV-2. Their antiviral activity was evaluated for the first time based on POM (Petra/Osiris/Molispiration) theory and docking analysis. POM calculation was used to analyze the atomic charge and geometric characteristics. The side effects, drug similarities, and drug scores were also assumed for the stable structure of each compound. These results correlated with the experimental values. The bioinformatics POM analyses of the relative antiviral activities of these derivatives are reported for the first time.

The COVID-19 pandemic caused by SARS-CoV-2 has majorly impacted public health and economies worldwide. Although several effective vaccines and drugs are now used to prevent and treat COVID-19, natural products, especially flavonoids, showed great therapeutic potential early in the pandemic and thus attracted particular attention. Quercetin, baicalein, baicalin, EGCG (epigallocatechin gallate), and luteolin are among the most studied flavonoids in this field. Flavonoids can directly or indirectly exert antiviral activities, such as the inhibition of virus invasion and the replication and inhibition of viral proteases. In addition, flavonoids can modulate the levels of interferon and proinflammatory factors. We have reviewed the previously reported relevant literature researching the pharmacological anti-SARS-CoV-2 activity of flavonoids where structures, classifications, synthetic pathways, and pharmacological effects are summarized. There is no doubt that flavonoids have great potential in the treatment of COVID-19. However, most of the current research is still in the theoretical stage. More studies are recommended to evaluate the efficacy and safety of flavonoids against SARS-CoV-2.

The recent pandemic of COVID-19 caused by the SARS-CoV-2 virus has brought upon the world an unprecedented challenge. During its acute dissemination, a rush for vaccines started, making the scientific community come together and contribute to the development of efficient therapeutic agents and vaccines. Natural products have been used as sources of individual molecules and extracts capable of inhibiting/neutralizing several microorganisms, including viruses. Natural extracts have shown effective results against the coronavirus family, when first tested in the outbreak of SARS-CoV-1, back in 2002. In this review, the relationship between natural extracts and SARS-CoV is discussed, while also providing insight into misinformation regarding the use of plants as possible therapeutic agents. Studies with plant extracts on coronaviruses are presented, as well as the main inhibition assays and trends for the future regarding the yet unknown long-lasting effects post-infection with SARS-CoV-2.

Inhibiting the main protease 3CLpro is the most common strategy in the search for antiviral drugs to fight the infection from SARS-CoV-2. We report that the natural compound eugenol is able to hamper in vitro the enzymatic activity of 3CLpro, the SARS-CoV-2 main protease, with an inhibition constant in the sub-micromolar range (Ki = 0.81 μM). Two phenylpropene analogs were also tested: the same effect was observed for estragole with a lower potency (Ki = 4.1 μM), whereas anethole was less active. The binding efficiency index of these compounds is remarkably favorable due also to their small molecular mass (MW < 165 Da). We envision that nanomolar inhibition of 3CLpro is widely accessible within the chemical space of simple natural compounds.