Luteolin Isolated from Juncus acutus L., a Potential Remedy for Human Coronavirus 229E.

The COVID-19 pandemic, caused by SARS-CoV-2, addressed the lack of specific antiviral drugs against coronaviruses. In this study, bioguided fractionation performed on both ethyl acetate and aqueous sub-extracts of Juncus acutus stems led to identifying luteolin as a highly active antiviral molecule against human coronavirus HCoV-229E. The apolar sub-extract (CH2Cl2) containing phenanthrene derivatives did not show antiviral activity against this coronavirus. Infection tests on Huh-7 cells, expressing or not the cellular protease TMPRSS2, using luciferase reporter virus HCoV-229E-Luc showed that luteolin exhibited a dose-dependent inhibition of infection. Respective IC50 values of 1.77 µM and 1.95 µM were determined. Under its glycosylated form (luteolin-7-O-glucoside), luteolin was inactive against HCoV-229E. Time of addition assay showed that utmost anti-HCoV-229E activity of luteolin was achieved when added at the post-inoculation step, indicating that luteolin acts as an inhibitor of the replication step of HCoV-229E. Unfortunately, no obvious antiviral activity for luteolin was found against SARS-CoV-2 and MERS-CoV in this study. In conclusion, luteolin isolated from Juncus acutus is a new inhibitor of alphacoronavirus HCoV-229E.

Clear polyurethane coatings with excellent virucidal properties: Preparation, characterization and rapid inactivation of human coronaviruses 229E and SARS-CoV-2.

Commercial polyurethane (PU) coating formulations have been modified with 1-(hydroxymethyl)-5,5-dimethylhydantoin (HMD) both in bulk (0.5 and 1% w/w) and onto the coatings surface as an N-halamine precursor, to obtain clear coatings with high virucidal activity. Upon immersion in diluted chlorine bleaching, the hydantoin structure on the grafted PU membranes was transformed into N-halamine groups, with a high surface chlorine concentration (40-43µg/cm2). Fourier transform infrared spectroscopy (FTIR) spectroscopy, thermogravimetric analysis (TGA), energy-dispersive X-ray (EDX), X-ray photoelectron spectroscopy (XPS) and iodometric titration were used to characterize the coatings and quantify the chlorine contents of the PU membranes after chlorination. Biological evaluation of their activity against Staphylococcus aureus (Gram-positive bacteria) and human coronaviruses HCoV-229E and SARS-CoV-2 was performed, and high inactivation of these pathogens was observed after short contact times. The inactivation of HCoV-229E was higher than 98% for all modified samples after just 30 minutes, whereas it was necessary 12 hours of contact time for complete inactivation of SARS-CoV-2. The coatings were fully rechargeable by immersion in diluted chlorine bleach (2% v/v) for at least 5 chlorination-dechlorination cycles. Moreover, the performance of the antivirus efficiency of the coatings is considered as long-lasting, because experiments of reinfection of the coatings with HCoV-229E coronavirus did not show any loss of the virucidal activity after three consecutive infection cycles without reactivation of the N-halamine groups.

Epidemiology of Non-SARS-CoV2 Human Coronaviruses (HCoVs) in People Presenting with Influenza-like Illness (ILI) or Severe Acute Respiratory Infections (SARI) in Senegal from 2012 to 2020.

In addition to emerging coronaviruses (SARS-CoV, MERS, SARS-CoV-2), there are seasonal human coronaviruses (HCoVs): HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1. With a wide distribution around the world, HCoVs are usually associated with mild respiratory disease. In the elderly, young children and immunocompromised patients, more severe or even fatal respiratory infections may be observed. In Africa, data on seasonal HCoV are scarce. This retrospective study investigated the epidemiology and genetic diversity of seasonal HCoVs during nine consecutive years of influenza-like illness surveillance in Senegal. Nasopharyngeal swabs were collected from ILI outpatients or from SARI hospitalized patients. HCoVs were diagnosed by qRT-PCR and the positive samples were selected for molecular characterization. Among 9337 samples tested for HCoV, 406 (4.3%) were positive: 235 (57.9%) OC43, 102 (25.1%) NL63, 58 (14.3%) 229E and 17 (4.2%) HKU1. The four types circulated during the study period and a peak was noted between November and January. Children under five were the most affected. Co-infections were observed between HCoV types (1.2%) or with other viruses (76.1%). Genetically, HCoVs types showed diversity. The results highlighted that the impact of HCoVs must be taken into account in public health; monitoring them is therefore particularly necessary both in the most sensitive populations and in animals.

Coronaviruses

The coronaviruses belong to the family Coronaviridae in the order Nidovirales. CoVs are found globally and infect a variety of animals, causing illnesses that range from gastrointestinal tract infections, encephalitis and demyelination;and can be fatal. Humans coronaviruses (hCoVs) have traditionally been associated with self-limiting upper respiratory tract infections and gastrointestinal tract infections. In recent years, however, it has become increasingly evident that the hCoVs can cause more severe lower respiratory tract infections such as bronchitis, pneumonia and even acute respiratory distress syndrome (ARDS), and can lead to death. Seven CoVs are known to infect humans, with the four "common cold” CoVs circulating globally on a yearly basis. The remaining three are more pathogenic and have resulted in outbreaks with high mortality rates. This review focussed on the three pathogenic CoVs. © 2022 Elsevier Inc. All rights reserved.

Household transmission of seasonal coronavirus infections: Results from the Flu Watch cohort study.

Background: In the context of the current coronavirus disease 2019 (COVID-19) pandemic, understanding household transmission of seasonal coronaviruses may inform pandemic control. We aimed to investigate what proportion of seasonal coronavirus transmission occurred within households, measure the risk of transmission in households, and describe the impact of household-related factors of risk of transmission. Methods: Using data from three winter seasons of the UK Flu Watch cohort study, we measured the proportion of symptomatic infections acquired outside and within the home, the household transmission risk and the household secondary attack risk for PCR-confirmed seasonal coronaviruses. We present transmission risk stratified by demographic features of households. Results: We estimated that the proportion of cases acquired outside the home, weighted by age and region, was 90.7% (95% CI 84.6- 94.5, n=173/195) and within the home was 9.3% (5.5-15.4, 22/195). Following a symptomatic coronavirus index case, 14.9% (9.8 - 22.1, 20/134) of households experienced symptomatic transmission to at least one other household member. Onward transmission risk ranged from 11.90% (4.84-26.36, 5/42) to 19.44% (9.21-36.49, 7/36) by strain. The overall household secondary attack risk for symptomatic cases was 8.00% (5.31-11.88, 22/275), ranging across strains from 5.10 (2.11-11.84, 5/98) to 10.14 (4.82- 20.11, 7/69). Median clinical onset serial interval was 7 days (IQR= 6-9.5). Households including older adults, 3+ children, current smokers, contacts with chronic health conditions, and those in relatively deprived areas had the highest transmission risks. Child index cases and male index cases demonstrated the highest transmission risks. Conclusion: Most seasonal coronaviruses appear to be acquired outside the household, with relatively modest risk of onward transmission within households. Transmission risk following an index case appears to vary by demographic household features, with potential overlap between those demonstrating the highest point estimates for seasonal coronavirus transmission risk and COVID-19 susceptibility and poor illness outcomes.

Structural basis of main proteases of HCoV-229E bound to inhibitor PF-07304814 and PF-07321332.

PF-07321332 and PF-07304814, inhibitors against SARS-CoV-2 developed by Pfizer, exhibit broad-spectrum inhibitory activity against the main protease (Mpro) from various coronaviruses. Structures of PF-07321332 or PF-07304814 in complex with Mpros of various coronaviruses reveal their inhibitory mechanisms against different Mpros. However, the structural information on the lower pathogenic coronavirus Mpro with PF-07321332 or PF-07304814 is currently scarce, which hinders our comprehensive understanding of the inhibitory mechanisms of these two inhibitors. Meanwhile, given that some immunocompromised individuals are still affected by low pathogenic coronaviruses, we determined the structures of lower pathogenic coronavirus HCoV-229E Mpro with PF-07321332 and PF-07304814, respectively, and analyzed and defined in detail the structural basis for the inhibition of HCoV-229E Mpro by both inhibitors. Further, we compared the crystal structures of multiple coronavirus Mpro complexes with PF-07321332 or PF-07304814 to illustrate the differences in the interaction of Mpros, and found that the inhibition mechanism of lower pathogenic coronavirus Mpro was more similar to that of moderately pathogenic coronaviruses. Our structural studies provide new insights into drug development for low pathogenic coronavirus Mpro, and provide theoretical basis for further optimization of both inhibitors to contain potential future coronaviruses.

Evaluation of Broad Anti-Coronavirus Activity of Autophagy-Related Compounds Using Human Airway Organoids.

To deal with the broad spectrum of coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that threaten human health, it is essential to not only drugs develop that target viral proteins but also consider drugs that target host proteins/cellular processes to protect them from being hijacked for viral infection and replication. To this end, it has been reported that autophagy is deeply involved in coronavirus infection. In this study, we used airway organoids to screen a chemical library of autophagic modulators to identify compounds that could potentially be used to fight against infections by a broad range of coronaviruses. Among the 80 autophagy-related compounds tested, cycloheximide and thapsigargin reduced SARS-CoV-2 infection efficiency in a dose-dependent manner. Cycloheximide treatment reduced the infection efficiency of not only six SARS-CoV-2 variants but also human coronavirus (HCoV)-229E and HCoV-OC43. Cycloheximide treatment also reversed viral infection-induced innate immune responses. However, even low-dose (1 µM) cycloheximide treatment altered the expression profile of ribosomal RNAs; thus, side effects such as inhibition of protein synthesis in host cells must be considered. These results suggest that cycloheximide has broad-spectrum anti-coronavirus activity in vitro and warrants further investigation.

Heparan Sulfate and Enoxaparin Interact at the Interface of the Spike Protein of HCoV-229E but Not with HCoV-OC43.

It is known that the spike protein of human coronaviruses can bind to a secondary receptor, or coreceptor, to facilitate the virus entry. While HCoV-229E uses human aminopeptidase N (hAPN) as a receptor, HCoV-OC43 binds to 9-O-acetyl-sialic acid (9-O-Ac-Sia), which is linked in a terminal way to the oligosaccharides that decorate glycoproteins and gangliosides on the surface of the host cell. Thus, evaluating the possible inhibitory activity of heparan sulfate, a linear polysaccharide found in animal tissues, and enoxaparin sodium on these viral strains can be considered attractive. Therefore, our study also aims to evaluate these molecules' antiviral activity as possible adsorption inhibitors against non-SARS-CoV. Once the molecules' activity was verified in in vitro experiments, the binding was studied by molecular docking and molecular dynamic simulations confirming the interactions at the interface of the spike proteins.

Surveillance of endemic coronaviruses during the COVID-19 pandemic in Iran, 2021-2022.

Background: Human coronaviruses (HCoVs) 229E, OC43, HKU1, and NL63 are common viruses that continuously circulate in the human population. Previous studies showed the circulation of HCoVs during the cold months in Iran. We studied the circulation of HCoVs during coronavirus disease 2019 (COVID-19) pandemic to find the impact of pandemic on the circulation of these viruses. Methods: As a cross-sectional survey conducted during 2021 to 2022, of all throat swabs sent to Iran National Influenza Center from patients with severe acute respiratory infection, 590 samples were selected to test for HCoVs using one-step real-time RT-PCR. Results: Overall, 28 out of 590 (4.7%) tested samples were found to be positive for at least one HCoVs. HCoV-OC43 was the most common (14/590 or 2.4%), followed by HCoV-HKU1 (12/590 or 2%) and HCoV-229E (4/590 or 0.6%), while HCoV-NL63 was not detected. HCoVs were detected in patients of all ages and throughout the study period with peaks in the cold months of the year. Conclusions: Our multicenter survey provides insight into the low circulation of HCoVs during the COVID-19 pandemic in Iran in 2021/2022. Hygiene habits and social distancing measures might have important role in decreasing of HCoVs transmission. We believe that surveillance studies are needed to track the pattern of HCoVs distributions and detect changes in the epidemiology of such viruses to set out strategies in order to timely control the future outbreaks of HCoVs throughout the nation.

Mouse models susceptible to HCoV-229E and HCoV-NL63 and cross protection from challenge with SARS-CoV-2.

Human coronavirus 229E (HCoV-229E) and NL63 (HCoV-NL63) are endemic causes of upper respiratory infections such as the "common cold" but may occasionally cause severe lower respiratory tract disease in the elderly and immunocompromised patients. There are no approved antiviral drugs or vaccines for these common cold coronaviruses (CCCoV). The recent emergence of COVID-19 and the possible cross-reactive antibody and T cell responses between these CCCoV and SARS-CoV-2 emphasize the need to develop experimental animal models for CCCoV. Mice are an ideal experimental animal model for such studies, but are resistant to HCoV-229E and HCoV-NL63 infections. Here, we generated 229E and NL63 mouse models by exogenous delivery of their receptors, human hAPN and hACE2 using replication-deficient adenoviruses (Ad5-hAPN and Ad5-hACE2), respectively. Ad5-hAPN- and Ad5-hACE2-sensitized IFNAR-/- and STAT1-/- mice developed pneumonia characterized by inflammatory cell infiltration with virus clearance occurring 7 d post infection. Ad5-hAPN- and Ad5-hACE2-sensitized mice generated virus-specific T cells and neutralizing antibodies after 229E or NL63 infection, respectively. Remdesivir and a vaccine candidate targeting spike protein of 229E and NL63 accelerated viral clearance of virus in these mice. 229E- and NL63-infected mice were partially protected from SARS-CoV-2 infection, likely mediated by cross-reactive T cell responses. Ad5-hAPN- and Ad5-hACE2-transduced mice are useful for studying pathogenesis and immune responses induced by HCoV-229E and HCoV-NL63 infections and for validation of broadly protective vaccines, antibodies, and therapeutics against human respiratory coronaviruses including SARS-CoV-2.

Outbreak of acute respiratory disease caused by human adenovirus type 7 and human coronavirus-229E in Zhejiang Province, China.

In 2019, an outbreak of pharyngoconjunctival fever (PCF) occurred at a swimming center in Zhejiang Province, China. A total of 97 (13.55%) of the 716 amateur swimmers had illnesses, with 24 patients (24.74%) hospitalized in the pediatric ward. Human adenovirus serotype 7 (HAdV-7) was isolated from one concentrated water from the swimming pool, and 20 of 97 positive cases without liver damage. This outbreak led to a nosocomial outbreak in the pediatric ward, in which 1 nurse had a fever and was confirmed to be adenovirus positive. The hexon, fiber, and penton genes from 20 outbreak cases, 1 water sample, and 1 nurse had 100% homology. Furthermore, 2 cases admitted to the pediatric ward, 2 parents, and 1 doctor were confirmed to be human coronaviruses (HCoV-229E) positive. Finally, all outbreak cases had fully recovered, regardless of a single infection (adenovirus or HCoV-229E) or coinfection of these two viruses simultaneously. Thus, PCF and acute respiratory disease outbreaks in Zhejiang were caused by the completely homologous type 7 adenovirus and HCoV-229E, respectively. The swimming pool water contaminated with HAdV-7 was most likely the source of the PCF outbreak, whereas nosocomial transmission might be the source of HCoV-229E outbreak.

Synthesis of Novel 1-Oxo-2,3,4-trisubstituted Tetrahydroisoquinoline Derivatives, Bearing Other Heterocyclic Moieties and Comparative Preliminary Study of Anti-Coronavirus Activity of Selected Compounds.

A series of novel 1-oxo-2,3,4-trisubstituted tetrahydroisoquinoline (THIQ) derivatives bearing other heterocyclic moieties in their structure were synthesized based on the reaction between homophthalic anhydride and imines. Initial studies were carried out to establish the anti-coronavirus activity of some of the newly obtained THIQ-derivatives against two strains of human coronavirus-229E and OC-43. Their antiviral activity was compared with that of their close analogues, piperidinones and thiomorpholinones, previously synthesized in our group, with aim to expand the range of the tested representative sample and to obtain valuable preliminary information about biological properties of a wider variety of compounds.

The clinical and virological features of two children's coinfections with human adenovirus type 7 and human coronavirus-229E virus.

Objective: Human adenovirus (HAdV) coinfection with other respiratory viruses is common, but adenovirus infection combined with human coronavirus-229E (HCoV-229E) is very rare. Study design and setting: Clinical manifestations, laboratory examinations, and disease severity were compared between three groups: one coinfected with HAdV-Ad7 and HCoV-229E, one infected only with adenovirus (mono-adenovirus), and one infected only with HCoV-229E (mono-HCoV-229E). Results: From July to August 2019, there were 24 hospitalized children: two were coinfected with HAdV-Ad7 and HCoV-229E, and 21 were infected with a single adenovirus infection. Finally, one 14-year-old boy presented with a high fever, but tested negative for HAdV-Ad7 and HCoV-229E. Additionally, three adult asymptotic cases with HCoV-229E were screened. No significant difference in age was found in the coinfection and mono-adenovirus groups (11 vs. 8 years, p = 0.332). Both groups had the same incubation period (2.5 vs. 3 days, p = 0.8302), fever duration (2.5 vs. 2.9 days, p = 0.5062), and length of hospital stay (7 vs. 6.76 days, p = 0.640). No obvious differences were found in viral loads between the coinfection and mono-adenovirus groups (25.4 vs. 23.7, p = 0.570), or in the coinfection and mono-HCoV-229E groups (32.9 vs. 30.06, p = 0.067). All cases recovered and were discharged from the hospital. Conclusion: HAdV-Ad7 and HCoV-229E coinfection in healthy children may not increase the clinical severity or prolong the clinical course. The specific interaction mechanism between the viruses requires further study.

Calibration of Methods for SARS-CoV-2 Environmental Surveillance: A Case Study from Northwest Tuscany.

The current pandemic has provided an opportunity to test wastewater-based epidemiology (WBE) as a complementary method to SARS-CoV-2 monitoring in the community. However, WBE infection estimates can be affected by uncertainty factors, such as heterogeneity in analytical procedure, wastewater volume, and population size. In this paper, raw sewage SARS-CoV-2 samples were collected from four wastewater treatment plants (WWTPs) in Tuscany (Northwest Italy) between February and December 2021. During the surveillance period, viral concentration was based on polyethylene glycol (PEG), but its precipitation method was modified from biphasic separation to centrifugation. Therefore, in parallel, the recovery efficiency of each method was evaluated at lab-scale, using two spiking viruses (human coronavirus 229E and mengovirus vMC0). SARS-CoV-2 genome was found in 80 (46.5%) of the 172 examined samples. Lab-scale experiments revealed that PEG precipitation using centrifugation had the best recovery efficiency (up to 30%). Viral SARS-CoV-2 load obtained from sewage data, adjusted by analytical method and normalized by population of each WWTP, showed a good association with the clinical data in the study area. This study highlights that environmental surveillance data need to be carefully analyzed before their use in the WBE, also considering the sensibility of the analytical methods.

Effects of immunophilin inhibitors and non-immunosuppressive analogs on coronavirus replication in human infection models.

Rationale: Human coronaviruses (HCoVs) seriously affect human health by causing respiratory diseases ranging from common colds to severe acute respiratory diseases. Immunophilins, including peptidyl-prolyl isomerases of the FK506-binding protein (FKBP) and the cyclophilin family, are promising targets for pharmaceutical inhibition of coronavirus replication, but cell-type specific effects have not been elucidated. FKBPs and cyclophilins bind the immunosuppressive drugs FK506 and cyclosporine A (CsA), respectively. Methods: Primary human bronchial epithelial cells (phBECs) were treated with CsA, Alisporivir (ALV), FK506, and FK506-derived non-immunosuppressive analogs and infected with HCoV-229E. RNA and protein were assessed by RT-qPCR and immunoblot analysis. Treatment with the same compounds was performed in hepatoma cells (Huh-7.5) infected with HCoV-229E expressing Renilla luciferase (HCoV-229E-RLuc) and the kidney cell line HEK293 transfected with a SARS-CoV-1 replicon expressing Renilla luciferase (SARS-CoV-1-RLuc), followed by quantification of luminescence as a measure of viral replication. Results: Both CsA and ALV robustly inhibited viral replication in all models; both compounds decreased HCoV-229E RNA in phBECs and reduced luminescence in HCoV-229E-RLuc-infected Huh7.5 and SARS-CoV-1-RLuc replicon-transfected HEK293. In contrast, FK506 showed inconsistent and less pronounced effects in phBECs while strongly affecting coronavirus replication in Huh-7.5 and HEK293. Two non-immunosuppressive FK506 analogs had no antiviral effect in any infection model. Conclusion: The immunophilin inhibitors CsA and ALV display robust anti-coronaviral properties in multiple infection models, including phBECs, reflecting a primary site of HCoV infection. In contrast, FK506 displayed cell-type specific effects, strongly affecting CoV replication in Huh7.5 and HEK293, but inconsistently and less pronounced in phBECs.

Potent Virucidal Activity In Vitro of Photodynamic Therapy with Hypericum Extract as Photosensitizer and White Light against Human Coronavirus HCoV-229E.

The emergent human coronavirus SARS-CoV-2 and its high infectivity rate has highlighted the strong need for new virucidal treatments. In this sense, the use of photodynamic therapy (PDT) with white light, to take advantage of the sunlight, is a potent strategy for decreasing the virulence and pathogenicity of the virus. Here, we report the virucidal effect of PDT based on Hypericum extract (HE) in combination with white light, which exhibits an inhibitory activity of the human coronavirus HCoV-229E on hepatocarcinoma Huh-7 cells. Moreover, despite continuous exposure to white light, HE has long durability, being able to maintain the prevention of viral infection. Given its potent in vitro virucidal capacity, we propose HE in combination with white light as a promising candidate to fight against SARS-CoV-2 as a virucidal compound.

An integrative analysis of Qingfei Paidu Decoction for its anti-HCoV-229E mechanism in cold and damp environment based on the pharmacokinetics, metabolomics and molecular docking technology.

BACKGROUND: The novel coronavirus pneumonia (COVID-19) has spread rapidly around the world. As a member against the epidemic, Qingfei Paidu Decoction (QFPDD) has been approved for the treatment of COVID-19 in China. However, its antiviral mechanism was still largely unclear. PURPOSE: An integrated strategy was used to explore the antiviral mechanisms of QFPDD in cold and damp environment, including pharmacokinetic (PK), network pharmacology, metabolomics and protein verification. METHODS: Firstly, the pharmacokinetic study of the prototype absorbed ingredients were analyzed by UHPLC-QqQ-MS. Secondly, the metabolomics analysis of the endogenous constituents was carried out. Based on the aforementioned results, an integrated network was constructed to identify the curative components, crucial endogenous differential metabolites and related pathways. Finally, the validation tests were implemented by molecular docking and western blotting (WB). RESULTS: According to the pharmacokinetic behaviors analysis of 31 components in vivo, the flavonoids presented more longer residence time and higher exposure compared with the other compounds. The efficacy and antiviral mechanism of QFPDD were verified by the poly-pharmacology, metabolomics, molecular docking and WB. For the occurrence of metabolic disorder, the change of amino acid transporters should not be neglected. Afterward, 8 curative compounds, 6 key genes and corresponding metabolic pathways were filtered by compound-reaction-enzyme-gene network. The molecular docking verified that the active ingredients bound to the relevant targets well. CONCLUSION: In the present study, an in vivo comprehensive pharmacokinetic behaviors of QFPDD was analyzed for the first time. The results illustrated that QFPDD could exhibit immune regulation, anti-infection, anti-inflammation and metabolic disorder to perform a corresponding therapeutic effect. Moreover, our findings highlighted the roles of amino acid transporters in the coronavirus infection situation.

Pulsed-Xenon Ultraviolet Light Highly Inactivates Human Coronaviruses on Solid Surfaces, Particularly SARS-CoV-2.

In the context of ongoing and future pandemics, non-pharmaceutical interventions are critical in reducing viral infections and the emergence of new antigenic variants while the population reaches immunity to limit viral transmission. This study provides information on efficient and fast methods of disinfecting surfaces contaminated with different human coronaviruses (CoVs) in healthcare settings. The ability to disinfect three different human coronaviruses (HCoV-229E, MERS-CoV, and SARS-CoV-2) on dried surfaces with light was determined for a fully characterized pulsed-xenon ultraviolet (PX-UV) source. Thereafter, the effectiveness of this treatment to inactivate SARS-CoV-2 was compared to that of conventional low-pressure mercury UVC lamps by using equivalent irradiances of UVC wavelengths. Under the experimental conditions of this research, PX-UV light completely inactivated the CoVs tested on solid surfaces since the infectivity of the three CoVs was reduced up to 4 orders of magnitude by PX-UV irradiation, with a cumulated dose of as much as 21.162 mJ/cm2 when considering all UV wavelengths (5.402 mJ/cm2 of just UVC light). Furthermore, continuous irradiation with UVC light was less efficient in inactivating SARS-CoV-2 than treatment with PX-UV light. Therefore, PX-UV light postulates as a promising decontamination measure to tackle the propagation of future outbreaks of CoVs.

Antiviral Activity of Ficus rubiginosa Leaf Extracts against HSV-1, HCoV-229E and PV-1.

Ficus rubiginosa plant extract showed antimicrobial activity, but no evidence concerning its antiviral properties was reported. The antiviral activity of the methanolic extract (MeOH) and its n-hexane (H) and ethyl acetate (EA) fractions against Herpes simplex virus-1 (HSV-1), Human coronavirus (HCoV) -229E, and Poliovirus-1 (PV-1) was investigated in the different phases of viral infection in the VERO CCL-81 cell line. To confirm the antiviral efficacy, a qPCR was conducted. The recorded cytotoxic concentration 50% was 513.1, 298.6, and 56.45 µg/mL for MeOH, H, and EA, respectively, assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay after 72 h of treatment. The Ficus rubiginosa leaf extract inhibited the replication of HSV-1 in the early stages of infection, showing a complete inhibition up to 0.62, 0.31, and 1.25 µg/mL. Against HCoV-229E, a total inhibition up to 1.25 µg/mL for MeOH and H as well as 5 µg/mL for EA was observed. Otherwise, no activity was recorded against PV-1. The leaf extract could act directly on the viral envelope, destructuring the lipid membrane and/or directly blocking the enriched proteins on the viral surface. The verified gene inhibition suggested that the treatments with M, H, and EA impaired HSV-1 and HCoV-229E replication, with a greater antiviral efficiency against HSV-1 compared to HCoV-229E, possibly due to a greater affinity of Ficus rubiginosa towards membrane glycoproteins and/or the different lipid envelopes.

Therapeutic Effect of Gegentang Granules on Mouse Model with hCoV-229E Pneumonia and Hanshi Yidu Xifei Syndrome

Objective：To determine the therapeutic effect of Gegentang granules on a disease-syndrome mouse model combining human coronavirus 229E（hCoV-229E）pneumonia with Hanshi Yidu Xifei syndrome in vivo. Method： Mice were randomly divided into normal group，infection group，cold-dampness group，model group，chloroquine phosphate group（0.18 g·kg-1），interferon-α2b（IFN-α2b）group（1.83×106 U·kg-1）， Gegentang granules high-dose and low-dose groups（6.6，3.3 g·kg-1）with 10 mice in each group. Cold-dampness environment and hCoV-229E infection were used for modeling，and the general status and lung index of mice in each group were observed. The viral load in lung tissue was detected by real-time fluorescent quantitative polymerase chain reaction（Real-time PCR），the pathological changes in lung tissue were evaluated by hematoxylin-eosin（HE）staining，the levels of serum gastrointestinal hormones and inflammatory factors in lung tissue were detected by enzyme-linked immunosorbent assay（ELISA），and the percentage of peripheral blood lymphocytes was detected by flow cytometry. Result：Comparing with model group，Gegentang granules could significantly alleviate the physical signs of Hanshi Yidu Xifei syndrome，including listlessness，weakness of limbs，sticky stool，etc. Comparing with model group，Gegentang granules high-dose group significantly reduced lung index，histopathological score of interstitial lung and bronchus，and the level of serum motilin（P< 0.05，P<0.01），two doses of Gegentang granules could significantly increase the level of serum gastrin（P< 0.05，P<0.01），the percentage of CD4+ ，CD8+ T lymphocytes in peripheral blood（P<0.05，P<0.01），and the level of tumor necrosis factor-α（TNF-α）in lung tissue was significantly decreased（P<0.01），and the level of interleukin-6（IL-6）showed decreasing tendency. Conclusion： Gegentang granules has therapeutic effect on model mice. It can improve the appearance and behavior characterization，regulate the level of gastrointestinal hormones，decrease lung index and histopathological score，and possibly play an immunomodulatory role by inhibiting the expression of inflammatory cytokines in lung tissue and restoring the percentage of peripheral blood lymphocytes. © 2022, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.