Progress in understanding the health promoting effect of egg yolk immunoglobulin

As an important immuneoactive component in eggs, yolk immunoglobulin (IgY) shows great competitiveness in research and production due to its good stability, high safety, low cost, easy availability, strong immune activity, and no drug resistance. This article highlights the significant advantages of IgY as a good antibiotic substitute in the prevention and treatment of viral and bacterial diseases. Also, IgY has great potential in the regulation of nutrient metabolism balance, intestinal microflora and immune homeostasis by affecting key rate-limiting enzymes, and relevant receptors and inflammatory factors specifically. Proper diet and targeted delivery of foodborne IgY may be a new perspective on inflammation regulation, disease control, nutritional balance or homeostasis, and oral microencapsulated IgY is expected to be a new approach against increasing public health emergencies (such as COVID-19 pandemic).

Proposed Convolution Architecture for Monkeypox Detection using Dermoscopy Images

Monkeypox is a skin disease that spreadsfrom animals to people and then people to people, the class of the monkeypox is zoonotic and its genus are othopoxvirus. There is no special treatment for monkeypox but the monkeypox and smallpox symptoms are almost similar, so the antiviral drug developed for prevent from smallpox virus may be used for monkeypox Infected person, the Prevention of monkeypox is just like COVID-19 proper hand wash, Smallpox vaccine, keep away from infected person, used PPE kits. In this paper Deep learning is use for detection of monkeypox with the help of CNN model, The Original Images contains a total number of 228 images, 102 belongs to the Monkeypox class and the remaining 126 represents the normal. But in deep learning greater amount of data required, data augmentation is also applied on it after this the total number of images are 3192. A variety of optimizers have been used to find out the best result in this paper, a comparison is usedbased on Loss, Accuracy, AUC, F1 score, Validation loss, Validation accuracy, validation AUC, Validation F1 score of each optimizer. after comparing alloptimizer, the Adam optimizer gives the best result its total testing accuracy is 92.21%, total number of epochs used for testing is 100. With the help of deep learning model Doctors are easily detect the monkeypox virus with the single image of infected person. © 2023 IEEE.

COVID-19 repellent cloth

In this research work, for the first time, we have developed and demonstrated a COVID-19 repellent coating on cotton cloth that not only repels the virus but also most of the human body fluids (superhemophobic). The coating was tested in the BSL3 lab. The controlled experiments revealed no significant increase in the log viral particles on coated fabric compared to the uncoated surface, evidence that the coated fabric resisted the SARS-CoV-2 inoculum. Further, the coated cloth exhibited excellent dust-free nature and stain resistance against body fluids (blood, urine, bovine serum, water, and saliva aerosol). It also shows sufficient robustness for repetitive usage. The fabrication process for the developed COVID-19 repellent cloth is simple and affordable and can be easily scaled up for mass production. Such coating could be applied on various surfaces, including daily clothes, masks, medical clothes, curtains, etc. The present finding could be a mammoth step towards controlling infection spread, including COVID-19.

Potential inhibition of Melaleuca leucadendron L. compounds against the NSP5 SARS CoV-2 protein

COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome (SARS-CoV-2), causing a global health emergency as a pandemic disease. The lack of certain drug molecules or treatment strategies to fight this disease makes it worse. Therefore, effective drug molecules are needed to fight COVID-19. Non Structural Protein (NSP5) or called Main Protease (Mpro) of SARS CoV 2, a key component of this viral replication, is considered a key target for anti-COVID-19 drug development. The purpose of this study is to determine whether the compounds in the Melaleuca leucadendron L. plant such as 1,8-cineole, terpene, guaiol, linalol, a-selinenol, beta-eudesmol and P-eudesmol are predicted to have antiviral activity for COVID-19. Interaction of compounds with NSP5 with PDB code 6WNP analyzed using molecular docking with Molegro Virtual Docker. Based on binding affinity, the highest potential as an anti-viral is Terpineol with binding energy (-119.743 kcal/mol). The results of the interaction showed that terpinol has similarities in all three amino acid residues namely Cys 145, Gly 143, and Glu 166 with remdesivir and native ligand. Melaleuca leucadendron L. may represent a potential herbal treatment to act as: COVID-19 NSP5, however these findings must be validated in vitro and in vivo.

Herbal remedies in post-COVID trauma: a systematic review

The world has faced huge challenges throughout the endemic of COVID-19. The survivors of Covid too are facing health difficulties. The non-availability of specific treatments made researchers search for all the possible treatment regimens including traditional medicines. India has the greatest culture of Ayurveda. Indian government's AYUSH ministry has granted permission for use of ancient systems of medicine for treatment of some of the COVID-19 cases, especially which are not at advanced stages. Along with this certain reports are there which have shown the positive outcomes of Ayurvedic treatment of COVID-19. However, it is more beneficial to build the immune system of the host from a large population and its health perspective to avoid widespread infection and control the potency of the infectious viral particles. A vaccine can offer protection by boosting specific immunity in the host at the same time non-specific ways to improve host immunity are suggestible. This has carved a path for the use of ancient Indian therapeutic methods such as Ayurveda and Yoga. Although there are many general articles where the home remedies have suggested but, more scientific references are required to document the ayurvedic medicines for Covid related ailments. In this review, an attempt is made to organize available evidences of usefulness of Ayurveda, Yoga, in COVID-19.

Effective Nasal Disinfection as an Overlooked Strategy in Our Fight against COVID-19.

Although the recent advent of a vaccine and other therapeutic aids in our fight against COVID-19 has brought us a step closer to controlling the pandemic, our fight is far from over. Handwashing, masks, and social distancing practices are considered reasonable measures to control the spread of the disease have been well accepted by government officials and public health officials despite scarce and conflicting scientific evidence. Taking into consideration the aforementioned measures, there is an additional perhaps overlooked practice that warrants our attention-nasal disinfection and hygiene.

Oral anti-viral therapy for early COVID-19 infection in patients with haematological malignancies: A multicentre prospective cohort.

High rates of lung failure have been reported in haematological patients after SARS-CoV2 infection. An early administration of monoclonal antibodies or anti-virals may improve the prognosis. Oral anti-virals may have a wider use independently of the genetic variations of the virus. Prospective data on anti-virals in haematological malignancies (HMs) are still lacking. Outpatients diagnosed with HM and early COVID-19 infection were prospectively treated with the oral anti-virals nirmatrelvir/ritonavir and molnupiravir. Incidence of lung failure, deaths and adverse events was analysed. Long-term outcome at third month was evaluated. Eighty-two outpatients were evaluable for the study objectives. All patients had been treated for their HM within 12 months. COVID-19-related lung failure was 23.1%. Active HM (aOR = 4.42; p = 0.038) and prolonged viral shedding (aOR = 1.04; p = 0.022) resulted independent predictors of severe infection. The vaccination with three to four doses (aOR = 0.02; p = 0.001) and with two doses (aOR = 0.06; p = 0.006) resulted protective. COVID-19-related deaths at 28 days were 6.1%. All-cause mortality at 90-day follow-up was 13.4% (n. 11) and included opportunistic infections and cardiovascular events. In conclusion, this approach reduced the incidence of lung failure and specific mortality compared to previous cohorts, but patients remain at high risk of further complications.

DHFR Inhibitors Display a Pleiotropic Anti-Viral Activity against SARS-CoV-2: Insights into the Mechanisms of Action.

During the COVID-19 pandemic, drug repurposing represented an effective strategy to obtain quick answers to medical emergencies. Based on previous data on methotrexate (MTX), we evaluated the anti-viral activity of several DHFR inhibitors in two cell lines. We observed that this class of compounds showed a significant influence on the virus-induced cytopathic effect (CPE) partly attributed to the intrinsic anti-metabolic activity of these drugs, but also to a specific anti-viral function. To elucidate the molecular mechanisms, we took advantage of our EXSCALATE platform for in-silico molecular modelling and further validated the influence of these inhibitors on nsp13 and viral entry. Interestingly, pralatrexate and trimetrexate showed superior effects in counteracting the viral infection compared to other DHFR inhibitors. Our results indicate that their higher activity is due to their polypharmacological and pleiotropic profile. These compounds can thus potentially give a clinical advantage in the management of SARS-CoV-2 infection in patients already treated with this class of drugs.

Glycyrrhizin inhibits swine acute diarrhea syndrome coronavirus infection via the HMGB1/TLR4/JNK signal pathway

Swine acute diarrhea syndrome coronavirus (SADS-CoV), a newly discovered enteric coronavirus, is the etiological agent that causes severe clinical diarrhea and intestinal pathological damage in piglets. In this study, Vero E6 and IPI-2I cells were pretreated with different concentrations of glycyrrhizin (GLY) for 2 hours, and then infected with different concentrations of SADSCoV, aiming to investigate the inhibitory effect of GLY on SADS-CoV. Western blot and TCID50 results revealed a significantly decreased N protein expression and viral titer, indicating that GLY can inhibit the infection of SADS-CoV. Vero E6 and IPI-2I cells were pretreated with different concentrations of GLY for 2 hours and infected with SADS-CoV. Western blot results showed that when the concentration of GLY was 0.8 mmol/L, the expression of N protein decreased significantly, indicating that GLY inhibited the invasion of the virus. At first, cells were treated with 0.4 mmol/L GLY, and cell samples were collected at 2 hours, 6 hours and 12 hours after being infected with SADS-CoV for analysis, and the expression of N protein were found to be significantly reduced at all points, indicating that GLY had a significant inhibitory effect on the replication of the virus. GLY is a competitive inhibitor of high mobility group box 1 (HMGB1), and the receptors of HMGB1 mainly include TLR4 and RAGE. Based on this fact, the mutant plasmid at the key sites of HMGB1 (C45S, C106S, C45/106S) and the siRNA of the RAGE receptor were transfected to Vero E6 cells and infected with SADS-CoV, and the cell supernatant and samples were harvested. The western blot and TCID50 results showed that the expression of N protein and the virus titer were decreased, suggesting that GLY exerts its function by affecting the binding of HMGB1/TLR4/RAGE during SADS-CoV infection. To further explore the signaling pathway through which GLY functions, Vero E6 and IPI-2I cells were inoculated with SADS-CoV, and cell samples were harvested, western blot was used to detect the changes of MAPK proteins. The results showed that the protein expression levels of p-p38, p-JNK and p-ERK were up-regulated in the early and late stages, indicating that the MAPK pathway was activated by SADS-CoV infection. Vero E6 and IPI-2I were pretreated with different concentrations of GLY and TLR4 inhibitor TAK for 2 hours and infected with SADS-CoV. Protein samples were harvested and analysed by western blot which showed a decreased p-JNK and N proteins, while other proteins showed no significant changes. These results indicated that GLY and TAK regulated the phosphorylation of JNK but did not regulate the phosphorylation of p38 and ERK. Also, Vero E6 cells were treated with HMGB1 antibody, the siRNA of HMGB1 and HMGB1 mutants plasmid, and infected with SADS-CoV. Protein samples were harvested, western blot results showed that phosphorylation of JNK decreased, indicating that HMGB1 affected JNK phosphorylation. Finally, Vero E6 and IPI-2I cells were pretreated with different concentrations of JNK inhibitor SP600125 to infect SADS-CoV, western blot, TCID50 and IFA results showed that the expression of N protein and virus titer, as well as virus replication were reduced, indicating that SP600125 inhibited virus replication. In conclusion, our results revealed that GLY can inhibit in vitro replication of SADS- CoV, mainly through the HMGB1/TLR4/JNK signaling pathway. The discovery of this pathway provides theoretical support for the research of novel anti-SADS-CoV drugs.

Calculation of Electrostatic Potential Field of Coronavirus S Proteins for Brownian Dynamics Simulations

The Brownian dynamics method can give insight into the initial stages of the interaction of antiviral drug molecules with the structural components of bacteria or viruses. RAM of conventional personal computer allows calculation of Brownian dynamics of interaction of antiviral drugs with individual coronavirus S protein. However, scaling up this approach for modeling the interaction of antiviral drugs with the whole virion consisting of thousands of proteins and lipids is difficult due to high requirements for computing resources. In the case of the Brownian dynamics method, the main amount of RAM in the calculations is occupied by an array of values of the virion electrostatic potential field. When the system is increased from one S protein to the whole virion, the volume of data increases significantly. The standard protocol for calculating Brownian dynamics uses a three-dimensional grid with a spatial step of 1°A to calculate the electrostatic potential field. In this work, we consider the possibility of increasing the grid spacing parameter for calculating the electrostatic potential field of individual coronavirus S proteins. In this case, the amount of RAM occupied by the electrostatic potential field is reduced, which makes it possible to use personal computers for calculations. We performed Brownian dynamics simulations of interaction of an antiviral photosensitizer molecule with S proteins of three coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2, and demonstrated that reduction of detalization of electrostatic potential field does not influence the results of Brownian dynamics much © The Authors 2022. This paper is published with open access at SuperFri.org

In-silico screening of plant-derived natural compounds for their anti-COVID-19 potential

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, in December 2019 and quickly spread across the worldwide. It becomes a global pandemic and risk to the healthcare system of almost every nation around the world. In this study thirty natural compounds of 19 Indian herbal plants were used to analyze their binding with eight proteins associated with COVID -19. Based on the molecular docking as well as ADMET analysis, isovitexin, glycyrrhizin, sitosterol, and piperine were identified as potential herbal medicine candidates. On comparing the binding affinity with Ivermectin, we have found that the inhibition potentials of the Trigonella foenum-graecum (fenugreek), Glycyrrhiza glabra (licorice), Tinospora cordifolia (giloy) and Piper nigrum (black pepper) are very promising with no side-effects.

Fostering home-grown response to COVID-19: development of improved traditional herbal medicines to WHO standards

Facing the unprecedented burden and rapid spread of the Covid-19 pandemic across the globe, responses from various regions have been exceptionally quick. Drug discovery has been essentially based on repurposing, particularly at the onset of the scourge. Several experimental models have been designed ranging from in vitro cell culture systems to nonhuman primates;however, each with advantages and limitations. It was revealed beside its detrimental consequences on health, economy and the society, Covid-19 has also provided opportunity to highlight the immense potential of traditional medicine as a valid alternative for addressing major health threat. The African traditional medicine has been instrumental for the control of the COVID-19 pandemic in the continent, in situation of extremely low vaccination coverage. For optimal and sustainable use of traditional medicine, we strongly recommend products be developed following the WHO standards, while taking into consideration sustainability, environmental protection and copyright issues surrounding the natural product-based drug research and development.

Anti-viral compounds from Jatropha curcas seed extract with anti-HIV-1 and anti-SARS-CoV-2 action

Many studies have dealt with the medicinal properties of Jatropha curcas;however, there are limited studies on the scope of its antiviral potential. This is a fact associated with the current challenges posed by HIV-AIDS and COVID-19, which has reinforced the need to expand the knowledge about its antiviral resource. Based on the search for natural products with anti-HIV-1 and anti-SARS-CoV-2 activities, this work analyzed the extract of J. curcas seed, the structure of the plant whose antiviral references were not found in the literature, and the compounds that can potentiate it as a candidate for herbal medicine. GC-MS analysis was used to screen for the active substances of the J. curcas seeds, and the literature was searched to find those with anti-HIV-1 and anti-SARS-CoV-2 indication. The results showed they have 27 compounds, of which glycerol 1-palmitate, stigmasterol and gamma-sitosterol were shown to have antiviral action in the literature. Regarding glycerol 1-palmitate, no detailed description of its antiviral action was found. Stigmasterol and gamma-sitosterol act as anti-HIV-1 and anti-SARS-CoV-2, respectively, inhibiting the reverse transcriptase of HIV-1, the proteases 3CLpro, PLpro and the spike proteins of SARS-CoV-2. However, despite the fact that the extract of J. curcas seeds consist of antiviral compounds that fight against the etiological agents of HIV-AIDS and COVID-19, it is concluded that there is a need to deepen this evidence, by in vitro and in vivo assays.

Ethnobotanical study on the use of medicinal plants with antiviral interest, case of SARS-CoV-19, in the region of Seraidi (Annaba, north-east Algeria)

The taxonomic diversity and the richness of the region of Seraidi (North-East Algeria) in medicinal plants, as well as the appearance of diseases of viral origin, in particular, the current pandemic of SARS-CoV-2, led us to the realization of an ethnobotanical survey of plants with antiviral interests. The survey was conducted based on a pre-established quiz, with 120 people from different categories of the population of Seraidi, with the aim of listing the medicinal plants used in the treatment of viral diseases and collecting as much information as possible on this subject. After analyzing, the information provided by the people interviewed, we listed 32 species belonging to 20 families, of which the Lamiaceae family is the most represented. Older women are the most affected by the use of plants;people without a higher intellectual level have the most knowledge about the use of plants with antiviral interest. The leaf is the most widely used organ, in the form of a decoction or infusion, administered orally.

Patients with interstitial lung disease are high-risk of COVID-19 morbidity with implications on access to early oral anti-viral treatments

Introduction/Aim: Patients with interstitial lung disease (ILD) are at higher risk of COVID-19 infection associated morbidity and mortality, and hence may benefit from early anti-viral therapy. The access criteria for early oral anti-viral therapies for COVID-19 varied in early 2022 due to limited supplies nationally. We created a live clinical database of ILD patients in a tertiary hospital setting, stratifying them by measurable risk factors and therefore accessibility by state or national criteria to anti-viral therapy. Method(s): A list of active ILD clinic patients was generated from the WEBPAS clinic database. Data on patient demographics, co-morbidities and immunosuppressive medications relevant to access to anti-viral medications via the PBS criteria and state-based criteria was gathered by medical records review. Demographic information included age, BMI, ethnicity, residential care living and rurality. Co-morbidity risk factors included congestive cardiac failure, neurological disease, diabetes mellitus, chronic kidney disease, liver cirrhosis, chronic lung disease and immunodeficiencies. Medications of relevance included glucocorticoids, steroid-sparing immunomodulators and chemotherapy. Combinations of the above risk factors equate to eligibility to treatment. Result(s): Between the data capture dates of 1 February 2021 and 31 January 2022, 526 patients were identified. Of these 457 fit the inclusion criteria. Median age was 71.4 years (range 20-92), ratio of F:M was 1.09. 11% of patients were on long term oxygen therapy. Commonest conditions were idiopathic pulmonary fibrosis (26.3%), connective-tissue disease ILD (18%) and sarcoidosis (13.4%). 92 (20%) of patients fit into 'moderate or severely immunocompromised' criteria. 346 (75%) of patients fit criteria for early anti-virals by the first iteration of PBS criteria. Using the second iteration of PBS criteria, 374 (82%) of the ILD patients fit criteria for early anti-viral treatment. Notably, some patients qualify for anti-virals on multiple eligibility PBS criteria. Conclusion(s): A large proportion of our ILD cohort is deemed 'high risk' for COVID-19 morbidity and would qualify for early anti-viral therapies (regardless of vaccination status).

In-silico studies of active phytochemicals from siddha medicinal herbs of karisalai chooranam against SARS-CoV-2 main protease (3 CLpro), RNA dependent RNA polymerase and angiotensin-converting enzyme II receptor

Aim: The contagious disease COVID 19 is a recently out-broken pandemic situation which threatens humankind all over the world. Siddha system of medicine is one of the traditional medical systems of India, which has provided a novel remedy for many epidemics like Dengue, Chicken guinea earlier. On evaluating the literature evidence and considering the mortality and severity of the disease, we have attempted to identify the possible inhibition of viral replication by "Karisalai Chooranam" - a polyherbal Siddha formulation which contains herbs like Karisalai (Wedelia chinensis), Thoodhuvelai (Solanum trilobatum), Musumusukai (Melothria maderaspatana) and Seeragam (Cuminum cyminum). The aim of this study was to identify the bioactive components present in Karisalai chooranam and pin down the components that inhibit COVID 19 protease by In Silico molecular docking analysis. Material and methods: The study was performed for the active compounds present in the herbs (Wedelia chinensis - Benzoic acid, Solanum trilobatum- Disogenin, Melothria maderaspatana- beta-sitosterol, Cuminum cyminum L- Coumaric acid and Limonene) with three potential targets, PDB id: 6LU7 3-chymotrypsin-like protease (3CLpro), PDB id: 6-NUR RNA dependent RNA polymerase and PDB id: 2AJF Angiotensin-converting enzyme II (ACE2) receptor using Autodock Vina. Key findings: The active phytocomponents present in "Karisalai chooranam" was found to inhibit the target 3CL proenzyme and hereby halt the formation of 16 non-structural proteins (nsp1-nsp16) that are highly essential for viral replication and there by prevents viral survival in the host environment. The phytocomponents also inhibited the target RNA dependent RNA polymerase (PDB)-6NUR RdRp which possess versatile action in mediating nonstructural protein (nsp 12) essential for viral replication. A significant binding against the target Angiotensin-converting enzyme II (ACE2) receptors - PDB- 2AJF was found which was recognized as a binding site for novel coronavirus to cause its pathogenesis. Among the five active components present in the herb, the binding ability of Disogenin and beta-sitosterol with COVID19 protease suggests a possible mechanism of protease inhibition and thus preventing viral replication. Significance: The results strongly suggest that phytocomponents of "Karisalai chooranam" may act as a potential therapeutic agent for the management of COVID-19 and related symptoms. Further, the efficacy of the active compounds should be tested in vitro before being recommended as a drug.

Antiviral activitiy of curcumin, demethoxycurcumin, bisdemethoxycurcumin and cyclocurcumin compounds of Curcuma longa against NSP3 on SARS-CoV-2

SARS-CoV-2 genome encodes two large polyproteins (pp), pp1a and pp1ab which are cleaved and transformed into a mature form by a protease, non-structural protein 3 (NSP3). NSP3 is encoded by open reading frame (ORF) 1a/b. Curcuma longa (C. longa) or turmeric has been documented to have antiviral effects. The aim of this study was to assess the viral activities of C. longa against SARS-CoV-2 focusing on its potency to inhibit viral replication by targeting NSP3. PubChem databases were used to obtain the metabolic profile of C. longa. The compound's interaction with nucleocapsid was analyzed using molecular docking with Molegro Virtual Docker. Bioinformatics analysis based on rerank score presents all compounds of C. longa have higher binding affinity than the native ligand with cyclocurcumin as the lowest score (-128.38 kcal/mol). This anti-viral activity was hypothesized from the similarity of hydrogen bonds with amino acid residues Ser 128 and Asn 40 as key residues present in Ribavirin. This study reveals that C. longa is the potential to be developed as an antiviral agent through replication inhibition in SARS-CoV-2 targeting its replication mediated by NSP3.

The use of Ephedra herbs in the treatment of COVID-19

Objective: Ephedra herbs are the only extant genus in its family, Ephedraceae, and order, Ephedrales. It has been prescribed in traditional medicine for improving headaches and respiratory infections. On the other hand, because the coronavirus disease 2019 (COVID-19) causes respiratory problems and COVID-19 pandemic is the most widespread outbreak that has affected humanity in the last century, the current review aims using literature search to investigate the effects of the Ephedra herbs compounds on COVID-19 to supply a reference for its clinical application in the inhibition and remedy of COVID-19. Materials and Methods: This review was performed using articles published in various databases, including Web of Science, PubMed, Scopus, and Google Scholar, without a time limit. For this paper, the following keywords were used: "Ephedra", "coronavirus disease 2019", "COVID-19", "Severe acute respiratory syndrome coronavirus 2" or "SARS CoV 2". Results: The results of this review show that the Ephedra herbs have effectiveness on COVID-19 and its compounds can bind to angiotensin-converting enzyme 2 (ACE2) with a high affinity and act as a blocker and prevent the binding of the virus. Conclusion: Some plants used in traditional medicine, including the Ephedra herbs, with their active compounds, can be considered a candidate with high potential for the control and prevention of COVID-19.

Hydrogen sulfide: physiological roles and therapeutic implications against COVID-19.

The COVID-19 pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) poses a major menace to economic and public health worldwide. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) are two host proteins that play an essential function in the entry of SARS-COV-2 into host cells. Hydrogen sulfide (H2S), a new gasotransmitter, has been shown to protect the lungs from potential damage through its anti-inflammatory, antioxidant, antiviral, and anti-aging effects. It is well known that H2S is crucial in controlling the inflammatory reaction and the pro-inflammatory cytokine storm. Therefore, it has been suggested that some H2S donors may help treat acute lung inflammation. Furthermore, recent research illuminates a number of mechanisms of action that may explain the antiviral properties of H2S. Some early clinical findings indicate a negative correlation between endogenous H2S concentrations and COVID-19 intensity. Therefore, reusing H2S-releasing drugs could represent a curative option for COVID-19 therapy.

In Vitro and In Vivo Therapeutic Potential of 6,6'-Dihydroxythiobinupharidine (DTBN) from Nuphar lutea on Cells and K18-hACE2 Mice Infected with SARS-CoV-2.

We have previously published research on the anti-viral properties of an alkaloid mixture extracted from Nuphar lutea, the major components of the partially purified mixture found by NMR analysis. These are mostly dimeric sesquiterpene thioalkaloids called thiobinupharidines and thiobinuphlutidines against the negative strand RNA measles virus (MV). We have previously reported that this extract inhibits the MV as well as its ability to downregulate several MV proteins in persistently MV-infected cells, especially the P (phospho)-protein. Based on our observation that the Nuphar extract is effective in vitro against the MV, and the immediate need that the coronavirus disease 2019 (COVID-19) pandemic created, we tested here the ability of 6,6'-dihydroxythiobinupharidine DTBN, an active small molecule, isolated from the Nuphar lutea extract, on COVID-19. As shown here, DTBN effectively inhibits SARS-CoV-2 production in Vero E6 cells at non-cytotoxic concentrations. The short-term daily administration of DTBN to infected mice delayed the occurrence of severe clinical outcomes, lowered virus levels in the lungs and improved survival with minimal changes in lung histology. The viral load on lungs was significantly reduced in the treated mice. DTBN is a pleiotropic small molecule with multiple targets. Its anti-inflammatory properties affect a variety of pathogens including SARS-CoV-2 as shown here. Its activity appears to target both pathogen specific (as suggested by docking analysis) as well as cellular proteins, such as NF-κB, PKCs, cathepsins and topoisomerase 2, that we have previously identified in our work. Thus, this combined double action of virus inhibition and anti-inflammatory activity may enhance the overall effectivity of DTBN. The promising results from this proof-of-concept in vitro and in vivo preclinical study should encourage future studies to optimize the use of DTBN and/or its molecular derivatives against this and other related viruses.