Rapid Virucidal Activity of Japanese Saxifraga Species-Derived Condensed Tannins against SARS-CoV-2, Influenza A Virus, and Human Norovirus Surrogate Viruses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (IAV), and norovirus are global threats to human health. The application of effective virucidal agents, which contribute to the inactivation of viruses on hands and environmental surfaces, is important to facilitate robust virus infection control measures. Naturally derived virucidal disinfectants have attracted attention owing to their safety and eco-friendly properties. In this study, we showed that multiple Japanese Saxifraga species-derived fractions demonstrated rapid, potent virucidal activity against the SARS-CoV-2 ancestral strain and multiple variant strains, IAV, and two human norovirus surrogates: feline calicivirus (FCV) and murine norovirus (MNV). Condensed tannins were identified as active chemical constituents that play a central role in the virucidal activities of these fractions. At a concentration of 25 µg/mL, the purified condensed tannin fraction Sst-2R induced significant reductions in the viral titers of the SARS-CoV-2 ancestral strain, IAV, and FCV (reductions of ≥3.13, ≥3.00, and 2.50 log10 50% tissue culture infective doses [TCID50]/mL, respectively) within 10 s of reaction time. Furthermore, at a concentration of 100 µg/mL, Sst-2R induced a reduction of 1.75 log10 TCID50/mL in the viral titers of MNV within 1 min. Western blotting and transmission electron microscopy analyses revealed that Sst-2R produced structural abnormalities in viral structural proteins and envelopes, resulting in the destruction of viral particles. Furthermore, Saxifraga species-derived fraction-containing cream showed virucidal activity against multiple viruses within 10 min. Our findings indicate that Saxifraga species-derived fractions containing condensed tannins can be used as disinfectants against multiple viruses on hands and environmental surfaces. IMPORTANCE SARS-CoV-2, IAV, and norovirus are highly contagious pathogens. The use of naturally derived components as novel virucidal/antiviral agents is currently attracting attention. We showed that fractions from extracts of Saxifraga species, in the form of a solution as well as a cream, exerted potent, rapid virucidal activities against SARS-CoV-2, IAV, and surrogates of human norovirus. Condensed tannins were found to play a central role in this activity. The in vitro cytotoxicity of the purified condensed tannin fraction at a concentration that exhibited some extent of virucidal activity was lower than that of 70% ethanol or 2,000 ppm sodium hypochlorite solution, which are popular virucidal disinfectants. Our study suggests that Saxifraga species-derived fractions containing condensed tannins can be used on hands and environmental surfaces as safe virucidal agents against multiple viruses.

Synthesis and Anti-Influenza Virus Effects of Novel Substituted Polycyclic Pyridone Derivatives Modified from Baloxavir.

In this work, a series of novel substituted polycyclic pyridone derivatives were designed and synthesized as potent anti-influenza agents. The cytopathic effect (CPE) assay and cytotoxicity assay indicated that all of the compounds possessed potent anti-influenza virus activity and relatively low cytotoxicity; some of them inhibited the replication of influenza A virus (IAV) at picomolar concentrations. Further studies revealed that, at a concentration of 3 nM, three compounds (10a, 10d, and 10g) could significantly reduce the M2 RNA amounts and M2 protein expression of IAV and inhibit the activity of RNA-dependent RNA polymerase (RdRp). Among them, (R)-12-(5H-dibenzo[a,d][7]annulen-5-yl)-7-hydroxy-3,4,12,12a-tetrahydro-1H-[1,4]oxazino[3,4-c]pyrido[2,1-f][1,2,4]triazine-6,8-dione (10a) was found to be a promising anti-influenza drug candidate with good human liver microsomal stability, as well as with better selectivity index and oral bioavailability than Baloxavir.

Antiviral effects of azithromycin: A narrative review.

Viral infections have a great impact on human health. The urgent need to find a cure against different viruses led us to investigations in a vast range of drugs. Azithromycin (AZT), classified as a macrolide, showed various effects on different known viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV), Zika, Ebola, Enterovirus (EVs) and Rhinoviruses (RVs), and Influenza A previously; namely, these viruses, which caused global concerns, are considered as targets for AZT different actions. Due to AZT background in the treatment of known viral infections mentioned above (which is described in this study), in the early stages of COVID-19 (a new zoonotic disease caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) development, AZT drew attention to itself due to its antiviral and immunomodulatory effects as a valuable candidate for COVID-19 treatment. AZT usage instructions for treating different viral infections have always been under observation, and COVID-19 is no exception. There are still debates about the use of AZT in COVID-19 treatment. However, eventually, novel researches convinced WHO to announce the discontinuation of AZT use (alone or in combination with hydroxychloroquine) in treating SARS-CoV-2 infection. This research aims to study the structure of all of the viruses mentioned above and the molecular and clinical effects of AZT against the virus.

Rosin Soap Exhibits Virucidal Activity.

Chemical methods of virus inactivation are used routinely to prevent viral transmission in both a personal hygiene capacity but also in at-risk environments like hospitals. Several virucidal products exist, including hand soaps, gels, and surface disinfectants. Resin acids, which can be derived from tall oil, produced from trees, have been shown to exhibit antibacterial activity. However, whether these products or their derivatives have virucidal activity is unknown. Here, we assessed the capacity of rosin soap to inactivate a panel of pathogenic mammalian viruses in vitro. We show that rosin soap can inactivate human enveloped viruses: influenza A virus (IAV), respiratory syncytial virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For IAV, rosin soap could provide a 100,000-fold reduction in infectivity. However, rosin soap failed to affect the nonenveloped encephalomyocarditis virus (EMCV). The inhibitory effect of rosin soap against IAV infectivity was dependent on its concentration but not on the incubation time or temperature. In all, we demonstrate a novel chemical inactivation method against enveloped viruses, which could be of use for preventing virus infections in certain settings. IMPORTANCE Viruses remain a significant cause of human disease and death, most notably illustrated through the current coronavirus disease 2019 (COVID-19) pandemic. Control of virus infection continues to pose a significant global health challenge to the human population. Viruses can spread through multiple routes, including via environmental and surface contamination, where viruses can remain infectious for days. Methods for inactivating viruses on such surfaces may help mitigate infection. Here, we present evidence identifying a novel virucidal product, rosin soap, which is produced from tall oil from coniferous trees. Rosin soap was able to rapidly and potently inactivate influenza virus and other enveloped viruses.

1,2,4-Triazolo[1,5-a]pyrimidines: Efficient one-step synthesis and functionalization as influenza polymerase PA-PB1 interaction disruptors.

In the search for new anti-influenza virus (IV) compounds, we have identified the 1,2,4-triazolo[1,5-a]pyrimidine (TZP) as a very suitable scaffold to obtain compounds able to disrupt IV RNA-dependent RNA polymerase (RdRP) PA-PB1 subunits heterodimerization. In this work, in order to acquire further SAR insights for this class of compounds and identify more potent derivatives, we designed and synthesized additional series of analogues to investigate the role of the substituents around the TZP core. To this aim, we developed four facile and efficient one-step procedures for the synthesis of 5-phenyl-, 6-phenyl- and 7-phenyl-2-amino-[1,2,4]triazolo[1,5-a]pyrimidines, and 2-amino-5-phenyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-ol. Two analogues having the ethyl carboxylate moiety at the C-2 position of the TZP were also prepared in good yields. Then, the scaffolds herein synthesized and two previous scaffolds were functionalized and evaluated for their anti-IAV activity, leading to the identification of compound 22 that showed both anti-PA-PB1 (IC50 = 19.5 µM) and anti-IAV activity (EC50 = 16 µM) at non-toxic concentrations, thus resulting among the most active TZP derivatives reported to date by us. A selection of the synthesized compounds, along with a set of in-house available analogues, was also tested against SARS-CoV-2. The most promising compound 49 from this series displayed an EC50 value of 34.47 µM, highlighting the potential of the TPZ scaffold in the search for anti-CoV agents.

IFN-λ1 Displays Various Levels of Antiviral Activity In Vitro in a Select Panel of RNA Viruses.

Type III interferons (lambda IFNs) are a quite new, small family of three closely related cytokines with interferon-like activity. Attention to IFN-λ is mainly focused on direct antiviral activity in which, as with IFN-α, viral genome replication is inhibited without the participation of immune system cells. The heterodimeric receptor for lambda interferons is exposed mainly on epithelial cells, which limits its possible action on other cells, thus reducing the likelihood of developing undesirable side effects compared to type I IFN. In this study, we examined the antiviral potential of exogenous human IFN-λ1 in cellular models of viral infection. To study the protective effects of IFN-λ1, three administration schemes were used: 'preventive' (pretreatment); 'preventive/therapeutic' (pre/post); and 'therapeutic' (post). Three IFN-λ1 concentrations (from 10 to 500 ng/mL) were used. We have shown that human IFN-λ1 restricts SARS-CoV-2 replication in Vero cells with all three treatment schemes. In addition, we have shown a decrease in the viral loads of CHIKV and IVA with the 'preventive' and 'preventive/therapeutic' regimes. No significant antiviral effect of IFN-λ1 against AdV was detected. Our study highlights the potential for using IFN-λ as a broad-spectrum therapeutic agent against respiratory RNA viruses.

Clinically Relevant Influenza Virus Evolution Reconstituted in a Human Lung Airway-on-a-Chip.

Human-to-human transmission of viruses, such as influenza viruses and coronaviruses, can promote virus evolution and the emergence of new strains with increased potential for creating pandemics. Clinical studies analyzing how a particular type of virus progressively evolves new traits, such as resistance to antiviral therapies, as a result of passing between different human hosts are difficult to carry out because of the complexity, scale, and cost of the challenge. Here, we demonstrate that spontaneous evolution of influenza A virus through both mutation and gene reassortment can be reconstituted in vitro by sequentially passaging infected mucus droplets between multiple human lung airway-on-a-chip microfluidic culture devices (airway chips). Modeling human-to-human transmission of influenza virus infection on chips in the continued presence of the antiviral drugs amantadine or oseltamivir led to the spontaneous emergence of clinically prevalent resistance mutations, and strains that were resistant to both drugs were identified when they were administered in combination. In contrast, we found that nafamostat, an inhibitor targeting host serine proteases, did not induce viral resistance. This human preclinical model may be useful for studying viral evolution in vitro and identifying potential influenza virus variants before they appear in human populations, thereby enabling preemptive design of new and more effective vaccines and therapeutics. IMPORTANCE The rapid evolution of viruses, such as influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is challenging the use and development of antivirals and vaccines. Studies of within-host viral evolution can contribute to our understanding of the evolutionary and epidemiological factors that shape viral global evolution as well as development of better antivirals and vaccines. However, little is known about how viral evolution of resistance to antivirals occurs clinically due to the lack of preclinical models that can faithfully model influenza infection in humans. Our study shows that influenza viral evolution through mutation or gene reassortment can be recapitulated in a human lung airway-on-a-chip (airway chip) microfluidic culture device that can faithfully recapitulate the influenza infection in vitro. This approach is useful for studying within-host viral evolution, evaluating viral drug resistance, and identifying potential influenza virus variants before they appear in human populations, thereby enabling the preemptive design of new and more effective vaccines and therapeutics.

Effects of Basic Amino Acids and Their Derivatives on SARS-CoV-2 and Influenza-A Virus Infection.

Amino acids have been implicated with virus infection and replication. Here, we demonstrate the effects of two basic amino acids, arginine and lysine, and their ester derivatives on infection of two enveloped viruses, SARS-CoV-2, and influenza A virus. We found that lysine and its ester derivative can efficiently block infection of both viruses in vitro. Furthermore, the arginine ester derivative caused a significant boost in virus infection. Studies on their mechanism of action revealed that the compounds potentially disturb virus uncoating rather than virus attachment and endosomal acidification. Our findings suggest that lysine supplementation and the reduction of arginine-rich food intake can be considered as prophylactic and therapeutic regimens against these viruses while also providing a paradigm for the development of broad-spectrum antivirals.

Zinc-Embedded Polyamide Fabrics Inactivate SARS-CoV-2 and Influenza A Virus.

Influenza A viruses (IAV) and SARS-CoV-2 can spread via liquid droplets and aerosols. Face masks and other personal protective equipment (PPE) can act as barriers that prevent the spread of these viruses. However, IAV and SARS-CoV-2 are stable for hours on various materials, which makes frequent and correct disposal of these PPE important. Metal ions embedded into PPE may inactivate respiratory viruses, but confounding factors such as adsorption of viruses make measuring and optimizing the inactivation characteristics difficult. Here, we used polyamide 6.6 (PA66) fibers containing embedded zinc ions and systematically investigated if these fibers can adsorb and inactivate SARS-CoV-2 and IAV H1N1 when woven into a fabric. We found that our PA66-based fabric decreased the IAV H1N1 and SARS-CoV-2 titer by approximately 100-fold. Moreover, we found that the zinc content and the virus inactivating property of the fabric remained stable over 50 standardized washes. Overall, these results provide insights into the development of reusable PPE that offer protection against RNA virus spread.

Chemical Probes for Blocking of Influenza A M2 Wild-type and S31N Channels.

We report on using the synthetic aminoadamantane-CH2-aryl derivatives 1-6 as sensitive probes for blocking M2 S31N and influenza A virus (IAV) M2 wild-type (WT) channels as well as virus replication in cell culture. The binding kinetics measured using electrophysiology (EP) for M2 S31N channel are very dependent on the length between the adamantane moiety and the first ring of the aryl headgroup realized in 2 and 3 and the girth and length of the adamantane adduct realized in 4 and 5. Study of 1-6 shows that, according to molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations, all bind in the M2 S31N channel with the adamantyl group positioned between V27 and G34 and the aryl group projecting out of the channel with the phenyl (or isoxazole in 6) embedded in the V27 cluster. In this outward binding configuration, an elongation of the ligand by only one methylene in rimantadine 2 or using diamantane or triamantane instead of adamantane in 4 and 5, respectively, causes incomplete entry and facilitates exit, abolishing effective block compared to the amantadine derivatives 1 and 6. In the active M2 S31N blockers 1 and 6, the phenyl and isoxazolyl head groups achieve a deeper binding position and high kon/low koff and high kon/high koff rate constants, compared to inactive 2-5, which have much lower kon and higher koff. Compounds 1-5 block the M2 WT channel by binding in the longer area from V27-H37, in the inward orientation, with high kon and low koff rate constants. Infection of cell cultures by influenza virus containing M2 WT or M2 S31N is inhibited by 1-5 or 1-4 and 6, respectively. While 1 and 6 block infection through the M2 block mechanism in the S31N variant, 2-4 may block M2 S31N virus replication in cell culture through the lysosomotropic effect, just as chloroquine is thought to inhibit SARS-CoV-2 infection.

Strong alkaline electrolyzed water efficiently inactivates SARS-CoV-2, other viruses, and Gram-negative bacteria.

Air spaces and material surfaces in a pathogen-contaminated environment can often be a source of infection to humans, and disinfection has become a common intervention focused on reducing the contamination levels. In this study, we examined the efficacy of SAIW, a unique electrolyzed water with chlorine-free, high pH, high concentration of dissolved hydrogen, and low oxygen reduction potential, for the inactivation of several viruses and bacteria. Infectivity assays revealed that initial viral titers of enveloped and non-enveloped viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, herpes simplex virus type 1, human coronavirus, feline calicivirus, and canine parvovirus, were reduced by 2.9- to 5.5-log10 within 30 s of SAIW exposure. Similarly, the culturability of three Gram-negative bacteria (Escherichia coli, Salmonella, and Legionella) dropped down by 1.9- to 4.9-log10 within 30 s of SAIW treatment. Mechanistically, treatment with SAIW was found to significantly decrease the binding and subsequent entry efficiencies of SARS-CoV-2 on Vero cells. Finally, we showed that this chlorine-free electrolytic ion water had no acute inhalation toxicity in mice, demonstrating that SAIW holds promise for a safer antiviral and antibacterial disinfectant.

Comparison of Antiviral Agents for Seasonal Influenza Outcomes in Healthy Adults and Children: A Systematic Review and Network Meta-analysis.

Importance: Antiviral treatment of influenza is recommended for patients with influenza-like illness during periods of community cocirculation of influenza viruses and SARS-CoV-2; however, questions remain about which treatment is associated with the best outcomes and fewest adverse events. Objective: To compare the efficacy and safety of neuraminidase inhibitors and the endonuclease inhibitor for the treatment of seasonal influenza among healthy adults and children. Data Sources: Medline, Embase, and the Cochrane Register of Clinical Trials were searched from inception to January 2020 (the last search was updated in October 2020). Study Selection: Included studies were randomized clinical trials conducted among patients of all ages with influenza treated with neuraminidase inhibitors (ie, oseltamivir, peramivir, zanamivir, or laninamivir) or an endonuclease inhibitor (ie, baloxavir) compared with other active agents or placebo. Data Extraction and Synthesis: Two investigators identified studies and independently abstracted data. Frequentist network meta-analyses were performed; relative ranking of agents was conducted using P-score probabilities. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations criteria. Data were analyzed in October 2020. Main Outcomes and Measures: The time to alleviation of influenza symptoms (TTAS), complications of influenza, and adverse events (total adverse events, nausea, and vomiting). Results: A total of 26 trials were identified that investigated antiviral drugs at high or low doses; these trials included 11 897 participants, among whom 6294 (52.9%) were men and the mean (SD) age was 32.5 (16.9) years. Of all treatments comparing with placebo in efficacy outcomes, high-quality evidence indicated that zanamivir was associated with the shortest TTAS (hazard ratio, 0.67; 95% CI, 0.58-0.77), while baloxavir was associated with the lowest risk of influenza-related complications (risk ratio [RR], 0.51; 95% CI, 0.32-0.80) based on moderate-quality evidence. In safety outcomes, baloxavir was associated with the lowest risk of total adverse events (RR, 0.84; 95% CI, 0.74-0.96) compared with placebo based on moderate-quality evidence. There was no strong evidence of associations with risk of nausea or vomiting among all comparisons, except for 75 mg oseltamivir, which was associated with greater occurrence of nausea (RR, 1.82; 95% CI, 1.38-2.41) and vomiting (RR, 1.88; 95% CI, 1.47-2.41). Conclusions and Relevance: In this systematic review and network meta-analysis, all 4 antiviral agents assessed were associated with shortening TTAS; zanamivir was associated with the shortest TTAS, and baloxavir was associated with reduced rate of influenza-related complications.

High-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro.

Influenza and other respiratory viruses present a significant threat to public health, national security, and the world economy, and can lead to the emergence of global pandemics such as from COVID-19. A barrier to the development of effective therapeutics is the absence of a robust and predictive preclinical model, with most studies relying on a combination of in vitro screening with immortalized cell lines and low-throughput animal models. Here, we integrate human primary airway epithelial cells into a custom-engineered 96-device platform (PREDICT96-ALI) in which tissues are cultured in an array of microchannel-based culture chambers at an air-liquid interface, in a configuration compatible with high resolution in-situ imaging and real-time sensing. We apply this platform to influenza A virus and coronavirus infections, evaluating viral infection kinetics and antiviral agent dosing across multiple strains and donor populations of human primary cells. Human coronaviruses HCoV-NL63 and SARS-CoV-2 enter host cells via ACE2 and utilize the protease TMPRSS2 for spike protein priming, and we confirm their expression, demonstrate infection across a range of multiplicities of infection, and evaluate the efficacy of camostat mesylate, a known inhibitor of HCoV-NL63 infection. This new capability can be used to address a major gap in the rapid assessment of therapeutic efficacy of small molecules and antiviral agents against influenza and other respiratory viruses including coronaviruses.

Ozone inactivation of airborne influenza and lack of resistance of respiratory syncytial virus to aerosolization and sampling processes.

Influenza and RSV are human viruses responsible for outbreaks in hospitals, long-term care facilities and nursing homes. The present study assessed an air treatment using ozone at two relative humidity conditions (RHs) in order to reduce the infectivity of airborne influenza. Bovine pulmonary surfactant (BPS) and synthetic tracheal mucus (STM) were used as aerosols protectants to better reflect the human aerosol composition. Residual ozone concentration inside the aerosol chamber was also measured. RSV's sensitivity resulted in testing its resistance to aerosolization and sampling processes instead of ozone exposure. The results showed that without supplement and with STM, a reduction in influenza A infectivity of four orders of magnitude was obtained with an exposure to 1.70 ± 0.19 ppm of ozone at 76% RH for 80 min. Consequently, ozone could be considered as a virucidal disinfectant for airborne influenza A. RSV did not withstand the aerosolization and sampling processes required for the use of the experimental setup. Therefore, ozone exposure could not be performed for this virus. Nonetheless, this study provides great insight for the efficacy of ozone as an air treatment for the control of nosocomial influenza A outbreaks.

A novel aqueous extract from rice fermented with Aspergillus oryzae and Saccharomyces cerevisiae possesses an anti-influenza A virus activity.

Human influenza virus infections occur annually worldwide and are associated with high morbidity and mortality. Hence, development of novel anti-influenza drugs is urgently required. Rice Power® extract developed by the Yushin Brewer Co. Ltd. is a novel aqueous extract of rice obtained via saccharization and fermentation with various microorganisms, such as Aspergillus oryzae, yeast [such as Saccharomyces cerevisiae], and lactic acid bacteria, possessing various biological and pharmacological properties. In our previous experimental screening with thirty types of Rice Power® extracts, we observed that the 30th Rice Power® (Y30) extract promoted the survival of influenza A virus-infected Madin-Darby canine kidney (MDCK) cells. Therefore, to identify compounds for the development of novel anti-influenza drugs, we aimed to investigate whether the Y30 extract exhibits anti-influenza A virus activity. In the present study, we demonstrated that the Y30 extract strongly promoted the survival of influenza A H1N1 Puerto Rico 8/34 (A/PR/8/34), California 7/09, or H3N2 Aichi 2/68 (A/Aichi/2/68) viruses-infected MDCK cells and inhibited A/PR/8/34 or A/Aichi/2/68 viruses infection and growth in the co-treatment and pre-infection experiments. The pre-treatment of Y30 extract on MDCK cells did not induce anti-influenza activity in the cell. The Y30 extract did not significantly affect influenza A virus hemagglutination, and neuraminidase and RNA-dependent RNA polymerase activities. Interestingly, the electron microscopy experiment revealed that the Y30 extract disrupts the integrity of influenza A virus particles by permeabilizing the viral membrane envelope, suggesting that Y30 extract has a direct virucidal effect against influenza A virus. Furthermore, we observed that compared to the ethyl acetate (EtOAc) extract, the water extract of Y30 extract considerably promoted the survival of cells infected with A/PR/8/34 virus. These results indicated that more anti-influenza components were present in the water extract of Y30 extract than in the EtOAc extract. Our results highlight the potential of a rice extract fermented with A. oryzae and S. cerevisiae as an anti-influenza medicine and a drug source for the development of anti-influenza compounds.

Disinfectant effectiveness against SARS-CoV-2 and influenza viruses present on human skin: model-based evaluation.

OBJECTIVES: Disinfection effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on human skin remains unclear because of the hazards of viral exposure. An evaluation model, which has been previously generated using human skin obtained from forensic autopsy samples, accurately mimics in vivo skin conditions for evaluating the effectiveness of disinfection against the virus. Using this model, we evaluated disinfection effectiveness against viruses on human skin. METHODS: Ethanol (EA), isopropanol (IPA), chlorhexidine gluconate (CHG) and benzalkonium chloride (BAC) were used as target disinfectants. First, disinfectant effectiveness against SARS-CoV-2 and influenza A virus (IAV) was evaluated in vitro. Disinfectant effectiveness against SARS-CoV-2 and IAV on human skin was then evaluated by titrating viruses present on the skin after applying each disinfectant on the skin for 5-60 seconds. RESULTS: Both, SARS-CoV-2 and IAV on human skin were completely inactivated within 5 seconds by 40%-80% EA and 70% IPA (log reduction values (LRVs) were >4). However, SARS-CoV-2 and IAV were barely inactivated by 20% EA (LRVs were <1). In vitro evaluation showed that, compared with EA and IPA, CHG and BAC were significantly inferior in terms of disinfection effectiveness. Conversely, the disinfection effectiveness of CHG and BAC against SARS-CoV-2 was higher on human skin than in vitro, and increased with increases in their concentration and reaction time (LRVs of 0.2% CHG/0.05% BAC were >2, and LRVs of 1.0% CHG/0.2% BAC were >2.5). CONCLUSIONS: Proper hand hygiene practices using alcohol-based disinfectants such as EA/IPA effectively inactivate SARS-CoV-2 and IAV on human skin.

Antiviral effect of fufang yinhua jiedu (FFYH) granules against influenza A virus through regulating the inflammatory responses by TLR7/MyD88 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang-Yinhua-Jiedu Granules (FFYH) optimized from a Yin-Qiao-San, as traditional Chinese medicine (TCM), was used to treat influenza and upper respiratory tract infection and was recommended for the prevention and treatment of SARS in 2003 and current COVID-19 in Anhui Province in 2020. AIM OF STUDY: In the clinical studies, FFYH was very effective for the treatment of influenza, but the mechanism of action against influenza A virus remains unclear. In the present study, we investigated the antiviral effect of FFYH against influenza A virus in vitro and vivo. Moreover, the potential mechanism of FFYH against influenza A virus in vivo was investigated for the first time. MATERIALS AND METHODS: CPE inhibition assay and HA assay were used to evaluate the in vitro antiviral effects of FFYH against influenza A virus H1N1, H3N2, H5N1, H7N9 and H9N2. Mice were used to evaluate the antiviral effect of FFYH in vivo with ribavirin and lianhuaqingwen as positive controls. RT-PCR was used to quantify the mRNA transcription of TNF-α, IL-6, IFN-γ, IP10, and IL-1ß mRNA. ELISA was used to examine the expression of inflammatory factors such as TNF-α, IL-6, IFN-γ, IP10, and IL-1ß in sera. The blood parameters were analyzed with auto hematology analyzer. Moreover, the potential mechanism of FFYH against influenza A virus in vivo was also investigated. RESULTS: FFYH showed a broad-spectrum of antiviral activity against H1N1, H3N2, H5N1, H7N9, and H9N2 influenza A viruses. Furthermore, FFYH dose-dependently increased the survival rate, significantly prolonged the median survival time of mice, and markedly reduced lung injury caused by influenza A virus. Also, FFYH significantly improve the sick signs, food taken, weight loss, blood parameters, lung index, and lung pathological changes. Moreover, FFYH could markedly inhibit the inflammatory cytokine expression of TNF-α, IL-6, IFN-γ, IP10, IL-10, and IL-1ß mRNA or protein via inhibition of the TLR7/MyD88/NF-κB signaling pathway in vivo. CONCLUSION: FFYH not only showed a broad-spectrum of anti-influenza virus activity in vitro, but also exhibited a significant protective effect against lethal influenza virus infection in vivo. Furthermore, our results indicated that the in vivo antiviral effect of FFYH against influenza virus may be attributed to suppressing the expression of inflammatory cytokines via regulating the TLR7/MyD88/NF-κB signaling pathway. These findings provide evidence for the clinical treatment of influenza A virus infection with FFYH.

Antiviral Bafilomycins from a Feces-Inhabiting Streptomyces sp.

A new bafilomycin derivative (1) and another seven known bafilomycins (2-8) were isolated from feces-derived Streptomyces sp. HTL16. The structure of 1 was elucidated by 1D and 2D NMR spectroscopic analysis. Biological testing demonstrated that these bafilomycins exhibited potent antiviral activities against the influenza A and SARS-CoV-2 viruses, with IC50 values in the nanomolar range, by inhibiting the activity of endosomal ATP-driven proton pumps.

Discovery of Potent SARS-CoV-2 Inhibitors from Approved Antiviral Drugs via Docking and Virtual Screening.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) pandemic continues to threaten patients, societies and healthcare systems around the world. There is an urgent need to search for possible medications. OBJECTIVE: This article intends to use virtual screening and molecular docking methods to find potential inhibitors from existing drugs that can respond to COVID-19. METHODS: To take part in the current research investigation and to define a potential target drug that may protect the world from the pandemic of corona disease, a virtual screening study of 129 approved drugs was carried out which showed that their metabolic characteristics, dosages used, potential efficacy and side effects are clear as they have been approved for treating existing infections. Especially 12 drugs against chronic hepatitis B virus, 37 against chronic hepatitis C virus, 37 against human immunodeficiency virus, 14 anti-herpesvirus, 11 anti-influenza, and 18 other drugs currently on the market were considered for this study. These drugs were then evaluated using virtual screening and molecular docking studies on the active site of the (SARS-CoV-2) main protease (6lu7). Once the efficacy of the drug is determined, it can be approved for its in vitro and in vivo activity against the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which can be beneficial for the rapid clinical treatment of patients. These drugs were considered potentially effective against SARS-CoV-2 and those with high molecular docking scores were proposed as novel candidates for repurposing. The N3 inhibitor cocrystallized with protease (6lu7) and the anti-HIV protease inhibitor Lopinavir were used as standards for comparison. RESULTS: The results suggest the effectiveness of Beclabuvir, Nilotinib, Tirilazad, Trametinib and Glecaprevir as potent drugs against SARS-CoV-2 since they tightly bind to its main protease. CONCLUSION: These promising drugs can inhibit the replication of the virus; hence, the repurposing of these compounds is suggested for the treatment of COVID-19. No toxicity measurements are required for these drugs since they were previously tested prior to their approval by the FDA. However, the assessment of these potential inhibitors as clinical drugs requires further in vivo tests of these drugs.