Leveraging opportunities for treatment/user simplicity (LOTUS): Navigating the current treatment landscape for achieving hepatitis C virus elimination among persons who inject drugs.

All-oral, direct-acting antivirals can cure hepatitis C virus (HCV) in almost all infected individuals; yet, many individuals with chronic HCV are not treated, and the incidence of acute HCV is increasing in some countries, including the United States. Strains on healthcare resources during the COVID-19 pandemic negatively impacted the progress toward the World Health Organization goal to eliminate HCV by 2030, especially among persons who inject drugs (PWID). Here, we present a holistic conceptual framework termed LOTUS (Leveraging Opportunities for Treatment/User Simplicity), designed to integrate the current HCV practice landscape and invigorate HCV treatment programs in the setting of endemic COVID-19: (A) treatment as prevention (especially among PWID), (B) recognition that HCV cure may be achieved with variable adherence with evidence supporting some forgiveness for missed doses, (C) treatment of all persons with active HCV infection (viremic), regardless of acuity, (D) minimal monitoring (MinMon) during treatment, and (E) rapid test and treat (TnT). The objective of this article is to review the current literature supporting each LOTUS petal; identify remaining gaps in knowledge or data; define the remaining barriers facing healthcare providers; and review evidence-based strategies for overcoming key barriers.

Repurposing of Plant-based Antiviral Molecules for the Treatment of COVID-19.

COVID-19, stemming from SARS-CoV-2, poses a formidable threat to global healthcare, with a staggering 77 million confirmed cases and 690,067 deaths recorded till December 24, 2023. Given the absence of specific drugs for this viral infection, the exploration of novel antiviral compounds becomes imperative. High-throughput technologies are actively engaged in drug discovery, and there is a parallel effort to repurpose plant-based molecules with established antiviral properties. In this context, the review meticulously delves into the potential of plant-based folk remedies and existing molecules. These substances have showcased substantial viral inhibition in diverse in vivo, in silico, and in vitro studies, particularly against critical viral protein targets, including SARS-CoV-2. The findings position these plant-based molecules as promising antiviral drug candidates for the swift advancement of treatments for COVID-19. It is noteworthy that the inherent attributes of these plant-based molecules, such as their natural origin, potency, safety, and cost-effectiveness, contribute to their appeal as lead candidates. The review advocates for further exploration through comprehensive in vivo studies conducted on animal models, emphasizing the potential of plant-based compounds to help in the ongoing quest to develop effective antivirals against COVID-19.

Arctigenin from Arctium lappa L. inhibits chikungunya virus by affecting its entry and replication.

BACKGROUND: Dengue and chikungunya, caused by dengue virus (DENV) and chikungunya virus (CHIKV) respectively, are the most common arthropod-borne viral diseases worldwide, for which there are no FDA-approved antivirals or effective vaccines. Arctigenin, a phenylpropanoid lignan from the seeds of Arctium lappa L. is known for its anti-inflammatory, anti-cancer, antibacterial, and immunomodulatory properties. Arctigenin's antimicrobial and immunomodulatory capabilities make it a promising candidate for investigating its potential as an anti-DENV and anti-CHIKV agent. PURPOSE: The aim of the study was to explore the anti-DENV and anti-CHIKV effects of arctigenin and identify the possible mechanisms of action. METHODS: The anti-DENV or anti-CHIKV effects of arctigenin was assessed using various in vitro and in silico approaches. Vero CCL-81 cells were infected with DENV or CHIKV and treated with arctigenin at different concentrations, temperature, and time points to ascertain the effect of the compound on virus entry or replication. In silico molecular docking was performed to identify the interactions of the compound with viral proteins. RESULTS: Arctigenin had no effects on DENV. Various time- and temperature-dependent assays revealed that arctigenin significantly reduced CHIKV RNA copy number and infectious virus particles and affected viral entry. Entry bypass assay revealed that arctigenin inhibited the initial steps of viral replication. In silico docking results revealed the high binding affinity of the compound with the E1 protein and the nsp3 macrodomain of CHIKV. CONCLUSION: This study demonstrates the in-vitro anti-CHIKV potential of arctigenin and suggests that the compound might affect CHIKV entry and replication. Further preclinical and clinical studies are needed to identify its safety and efficacy as an anti-CHIKV drug.

Antiviral, Cytoprotective, and Anti-Inflammatory Effect of Ampelozizyphus amazonicus Ducke Ethanolic Wood Extract on Chikungunya Virus Infection.

Chikungunya fever, a debilitating disease caused by Chikungunya virus (CHIKV), is characterized by a high fever of sudden onset and an intense arthralgia that impairs individual regular activities. Although most symptoms are self-limited, long-term persistent arthralgia is observed in 30-40% of infected individuals. Currently, there is no vaccine or specific treatment against CHIKV infection, so there is an urgent need for the discovery of new therapeutic options for CHIKF chronic cases. This present study aims to test the antiviral, cytoprotective, and anti-inflammatory activities of an ethanol extract (FF72) from Ampelozizyphus amazonicus Ducke wood, chemically characterized using mass spectrometry, which indicated the major presence of dammarane-type triterpenoid saponins. The major saponin in the extract, with a deprotonated molecule ion m/z 897 [M-H]-, was tentatively assigned as a jujubogenin triglycoside, a dammarane-type triterpenoid saponin. Treatment with FF72 resulted in a significant reduction in both virus replication and the production of infective virions in BHK-21-infected cells. The viability of infected cells was assessed using an MTT, and the result indicated that FF72 treatment was able to revert the toxicity mediated by CHIKV infection. In addition, FF72 had a direct effect on CHIKV, since the infectivity was completely abolished in the presence of the extract. FF72 treatment also reduced the expression of the major pro-inflammatory mediators overexpressed during CHIKV infection, such as IL-1ß, IL-6, IL-8, and MCP-1. Overall, the present study elucidates the potential of FF72 to become a promising candidate of herbal medicine for alphaviruses infections.

Glycyrrhiza glabra L. Extracts and Other Therapeutics against SARS-CoV-2 in Central Eurasia: Available but Overlooked.

In Central Eurasia, the availability of drugs that are inhibitors of the SARS-CoV-2 virus and have proven clinical efficacy is still limited. The aim of this study was to evaluate the activity of drugs that were available in Kazakhstan during the acute phase of the epidemic against SARS-CoV-2. Antiviral activity is reported for Favipiravir, Tilorone, and Cridanimod, which are registered drugs used for the treatment of respiratory viral infections in Kazakhstan. A licorice (Glycyrrhiza glabra) extract was also incorporated into this study because it offered an opportunity to develop plant-derived antivirals. The Favipiravir drug, which had been advertised in local markets as an anti-COVID cure, showed no activity against SARS-CoV-2 in cell cultures. On the contrary, Cridanimod showed impressive high activity (median inhibitory concentration 66 µg/mL) against SARS-CoV-2, justifying further studies of Cridanimod in clinical trials. Tilorone, despite being in the same pharmacological group as Cridanimod, stimulated SARS-CoV-2 replication in cultures. The licorice extract inhibited SARS-CoV-2 replication in cultures, with a high median effective concentration of 16.86 mg/mL. Conclusions: The synthetic, low-molecular-weight compound Cridanimod suppresses SARS-CoV-2 replication at notably low concentrations, and this drug is not toxic to cells at therapeutic concentrations. In contrast to its role as an inducer of interferons, Cridanimod is active in cells that have a genetic defect in interferon production, suggesting a different mechanism of action. Cridanimod is an attractive drug for inclusion in clinical trials against SARS-CoV-2 and, presumably, other coronaviruses. The extract from licorice shows low activity against SARS-CoV-2. At the same time, high doses of 2 g/kg of this plant extract show little or no acute toxicity in animal studies; for this reason, licorice products can still be considered for further development as a safe, orally administered adjunctive therapy.

Mechanistic Understanding of the Antiviral Properties of Pistachios and Zeaxanthin against HSV-1.

The search for alternative clinical treatments to fight resistance and find alternative antiviral treatments for the herpes simplex virus (HSV) is of great interest. Plants are rich sources of novel antiviral, pharmacologically active agents that provide several advantages, including reduced side effects, less resistance, low toxicity, and different mechanisms of action. In the present work, the antiviral activity of Californian natural raw (NRRE) and roasted unsalted (RURE) pistachio polyphenols-rich extracts was evaluated against HSV-1 using VERO cells. Two different extraction methods, with or without n-hexane, were used. Results showed that n-hexane-extracted NRRE and RURE exerted an antiviral effect against HSV-1, blocking virus binding on the cell surface, affecting viral DNA synthesis as well as accumulation of ICP0, UL42, and Us11 viral proteins. Additionally, the identification and quantification of phenolic compounds by RP-HPLC-DAD confirmed that extraction with n-hexane exclusively accumulated tocopherols, carotenoids, and xanthophylls. Amongst these, zeaxanthin exhibited strong antiviral activity against HSV-1 (CC50: 16.1 µM, EC50 4.08 µM, SI 3.96), affecting both the viral attachment and penetration and viral DNA synthesis. Zeaxanthin is a dietary carotenoid that accumulates in the retina as a macular pigment. The use of pistachio extracts and derivates should be encouraged for the topical treatment of ocular herpetic infections.

Kaempferol inhibits SARS-CoV-2 invasion by impairing heptad repeats-mediated viral fusion.

BACKGROUND: The continuous evolution of SARS-CoV-2 has underscored the development of broad-spectrum prophylaxis. Antivirals targeting the membrane fusion process represent promising paradigms. Kaempferol (Kae), an ubiquitous plant flavonol, has been shown efficacy against various enveloped viruses. However, its potential in anti-SARS-CoV-2 invasion remains obscure. PURPOSE: To evaluate capabilities and mechanisms of Kae in preventing SARS-CoV-2 invasion. METHODS: To avoid interference of viral replication, virus-like particles (VLPs) constructed with luciferase reporter were applied. To investigate the antiviral potency of Kae, human induced pluripotent stem cells (hiPSC)-derived alveolar epithelial cells type II (AECII) and human ACE2 (hACE2) transgenic mice were utilized as in vitro and in vivo models, respectively. Using dual split protein (DSP) assays, inhibitory activities of Kae in viral fusion were determined in Alpha, Delta and Omicron variants of SARS-CoV-2, as well as in SARS-CoV and MERS-CoV. To further reveal molecular determinants of Kae in restricting viral fusion, synthetic peptides corresponding to the conserved heptad repeat (HR) 1 and 2, involved in viral fusion, and the mutant form of HR2 were explored by circular dichroism and native polyacrylamide gel electrophoresis. RESULTS: Kae inhibited SARS-CoV-2 invasion both in vitro and in vivo, which was mainly attributed to its suppressive effects on viral fusion, but not endocytosis, two pathways that mediate viral invasion. In accordance with the proposed model of anti-fusion prophylaxis, Kae functioned as a pan-inhibitor of viral fusion, including three emerged highly pathogenic coronaviruses, and the currently circulating Omicron BQ.1.1 and XBB.1 variants of SARS-CoV-2. Consistent with the typical target of viral fusion inhibitors, Kae interacted with HR regions of SARS-CoV-2 S2 subunits. Distinct from previous inhibitory fusion peptides which prevent the formation of six-helix bundle (6-HB) by competitively interacting with HRs, Kae deformed HR1 and directly reacted with lysine residues within HR2 region, the latter of which was considered critical for the preservation of stabilized S2 during SARS-CoV-2 invasion. CONCLUSIONS: Kae prevents SARS-CoV-2 infection by blocking membrane fusion and possesses a broad-spectrum anti-fusion ability. These findings provide valuable insights into potential benefits of Kae-containing botanical products as a complementary prophylaxis, especially during the waves of breakthrough infections and re-infections.

Harnessing and bioprospecting botanical-based herbal medicines against potential drug targets for COVID-19: a review coupled molecular docking studies.

Since the end of February 2020, the world has come to a standstill due to the virus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Since then, the global scientific community has explored various remedies and treatments against this virus, including natural products that have always been a choice because of their many benefits. Various known phytochemicals are well documented for their antiviral properties. Research is being carried out to discover new natural plant products or existing ones as a treatment measure for this disease. The three important targets in this regard are-papain like protease (PLpro), spike protein, and 3 chymotrypsin like proteases (3CLpro). Various docking studies are also being elucidated to identify the phytochemicals that modulate crucial proteins of the virus. The paper is simultaneously a comprehensive review that covers recent advances in the domain of the effect of various botanically derived natural products as an alternative treatment approach against Coronavirus Disease 2019 (COVID-19). Furthermore, the docking analyses revealed that rutin (inhibitor of the major protease of SARS-CoV-2), gallocatechin (e.g., interacting with 03 hydrogen bonds with a spike-like protein), lycorine (showing the best binding affinity with amino acids GLN498, THR500 and GLY446 of the spike-like protein), and quercetrin (inhabiting at its residues ASP216, PHE219, and ILE259) are promising inhibitors of SARS­CoV­2.Communicated by Ramaswamy H. Sarma.

Plants as Biofactories for Therapeutic Proteins and Antiviral Compounds to Combat COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a profound impact on the world's health and economy. Although the end of the pandemic may come in 2023, it is generally believed that the virus will not be completely eradicated. Most likely, the disease will become an endemicity. The rapid development of vaccines of different types (mRNA, subunit protein, inactivated virus, etc.) and some other antiviral drugs (Remdesivir, Olumiant, Paxlovid, etc.) has provided effectiveness in reducing COVID-19's impact worldwide. However, the circulating SARS-CoV-2 virus has been constantly mutating with the emergence of multiple variants, which makes control of COVID-19 difficult. There is still a pressing need for developing more effective antiviral drugs to fight against the disease. Plants have provided a promising production platform for both bioactive chemical compounds (small molecules) and recombinant therapeutics (big molecules). Plants naturally produce a diverse range of bioactive compounds as secondary metabolites, such as alkaloids, terpenoids/terpenes and polyphenols, which are a rich source of countless antiviral compounds. Plants can also be genetically engineered to produce valuable recombinant therapeutics. This molecular farming in plants has an unprecedented opportunity for developing vaccines, antibodies, and other biologics for pandemic diseases because of its potential advantages, such as low cost, safety, and high production volume. This review summarizes the latest advancements in plant-derived drugs used to combat COVID-19 and discusses the prospects and challenges of the plant-based production platform for antiviral agents.

Arsenic in medicine: past, present and future.

Arsenicals are one of the oldest treatments for a variety of human disorders. Although infamous for its toxicity, arsenic is paradoxically a therapeutic agent that has been used since ancient times for the treatment of multiple diseases. The use of most arsenic-based drugs was abandoned with the discovery of antibiotics in the 1940s, but a few remained in use such as those for the treatment of trypanosomiasis. In the 1970s, arsenic trioxide, the active ingredient in a traditional Chinese medicine, was shown to produce dramatic remission of acute promyelocytic leukemia similar to the effect of all-trans retinoic acid. Since then, there has been a renewed interest in the clinical use of arsenicals. Here the ancient and modern medicinal uses of inorganic and organic arsenicals are reviewed. Included are antimicrobial, antiviral, antiparasitic and anticancer applications. In the face of increasing antibiotic resistance and the emergence of deadly pathogens such as the severe acute respiratory syndrome coronavirus 2, we propose revisiting arsenicals with proven efficacy to combat emerging pathogens. Current advances in science and technology can be employed to design newer arsenical drugs with high therapeutic index. These novel arsenicals can be used in combination with existing drugs or serve as valuable alternatives in the fight against cancer and emerging pathogens. The discovery of the pentavalent arsenic-containing antibiotic arsinothricin, which is effective against multidrug-resistant pathogens, illustrates the future potential of this new class of organoarsenical antibiotics.

Global Challenges with Oral Antivirals for COVID-19.

Oral antivirals for COVID-19 can be game changers in low- and middle-income countries (LMICs). Challenges that may hinder current and future oral antiviral rollouts span use in special populations, drug-drug and herb-drug interactions, adverse events, development of resistance, black markets, and equity in access and prescribing. Future antivirals may address some of these barriers; however, health systems around the world should be equipped to receive and administer COVID-19 oral antivirals. Improvements in manufacturing capacity, community engagement, capacity for testing and linkage to care, and systems for surveillance and safety monitoring could "change the game" for LMICs, irrespective of any specific antiviral drug. Investments in health care infrastructure can promote resilience, not only for COVID-19 but also for future local and global health crises.

The Novel hDHODH Inhibitor MEDS433 Prevents Influenza Virus Replication by Blocking Pyrimidine Biosynthesis.

The pharmacological management of influenza virus (IV) infections still poses a series of challenges due to the limited anti-IV drug arsenal. Therefore, the development of new anti-influenza agents effective against antigenically different IVs is therefore an urgent priority. To meet this need, host-targeting antivirals (HTAs) can be evaluated as an alternative or complementary approach to current direct-acting agents (DAAs) for the therapy of IV infections. As a contribution to this antiviral strategy, in this study, we characterized the anti-IV activity of MEDS433, a novel small molecule inhibitor of the human dihydroorotate dehydrogenase (hDHODH), a key cellular enzyme of the de novo pyrimidine biosynthesis pathway. MEDS433 exhibited a potent antiviral activity against IAV and IBV replication, which was reversed by the addition of exogenous uridine and cytidine or the hDHODH product orotate, thus indicating that MEDS433 targets notably hDHODH activity in IV-infected cells. When MEDS433 was used in combination either with dipyridamole (DPY), an inhibitor of the pyrimidine salvage pathway, or with an anti-IV DAA, such as N4-hydroxycytidine (NHC), synergistic anti-IV activities were observed. As a whole, these results indicate MEDS433 as a potential HTA candidate to develop novel anti-IV intervention approaches, either as a single agent or in combination regimens with DAAs.

Barriers and facilitators related to HCV treatment uptake among HIV coinfected populations in Canada: Patient and treatment provider perceptions.

BACKGROUND: Direct-acting antiviral (DAA) uptake is challenging across HIV-hepatitis C (HCV) coinfected populations. This study sought to identify barriers and facilitators related to DAA uptake in priority populations in Canada. METHODS: This qualitative descriptive study included 11 people living with HIV with a history of HCV and 15 HCV care providers. Participants were part of either nominal groups (n = 4) or individual interviews (n = 6) in which they identified and ranked barriers and facilitators to DAA uptake. Consolidated lists of barriers and facilitators were identified thematically. RESULTS: Patient participants highly ranked the following barriers: competing priorities and needs (ie, social instability and mental health), delays in care, lack of adherence, and polypharmacy. Provider participant top barriers were the following: competing priorities and needs (ie, social chaos), delays in care (eg, systemic barriers, difficulties engaging patients, lack of trained HCV providers), and HCV-related stigma. Patient participants identified having a strong network of health care providers, family, and friends, possessing intrinsic motivation, and DAAs being a simple and tolerable oral treatment as important facilitators. Provider participant top-ranked facilitators were having resources to identify hard-to-reach populations (eg, patient navigation, outreach), holistic care and addiction management, provider HCV education, and a strong network of interprofessional collaboration. CONCLUSION: The barriers to DAA initiation addressed by patients and providers overlapped, with some nuances. Multidisciplinary care fostering a strong supportive network and intrinsically motivated patients along with HCV education emerged as key facilitators. This study provides insights for developing potential strategies to improve DAA uptake among HIV-HCV coinfected people in Canada.

Broad-spectrum antiviral activity of Spatholobus suberectus Dunn against SARS-CoV-2, SARS-CoV-1, H5N1, and other enveloped viruses.

The current COVID-19 pandemic caused by SARS-Cov-2 is responsible for more than 6 million deaths globally. The development of broad-spectrum and cost-effective antivirals is urgently needed. Medicinal plants are renowned as a complementary approach in which antiviral natural products have been established as safe and effective drugs. Here, we report that the percolation extract of Spatholobus suberectus Dunn (SSP) is a broad-spectrum viral entry inhibitor against SARS-CoV-1/2 and other enveloped viruses. The viral inhibitory activities of the SSP were evaluated by using pseudotyped SARS-CoV-1 and 2, HIV-1ADA and HXB2 , and H5N1. SSP effectively inhibited viral entry and with EC50 values ranging from 3.6 to 5.1 µg/ml. Pre-treatment of pseudovirus or target cells with SSP showed consistent inhibitory activities with the respective EC50 value of 2.3 or 2.1 µg/ml. SSP blocked both SARS-CoV-2 spike glycoprotein and the host ACE2 receptor. In vivo studies indicated that there was no abnormal toxicity and behavior in long-term SSP treatment. Based on these findings, we concluded that SSP has the potential to be developed as a drug candidate for preventing and treating COVID-19 and other emerging enveloped viruses.

Promising natural products against SARS-CoV-2: Structure, function, and clinical trials.

The corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus type 2 (SARS-COV-2) poses a severe threat to human health and still spreads globally. Due to the high mutation ratio and breakthrough infection rate of the virus, vaccines and anti-COVID-19 drugs require continual improvements. Drug screening research has shown that some natural active products can target the critical proteins of SARS-CoV-2, including 3CLpro, ACE2, FURIN, and RdRp, which could produce great inhibitory effects on SARS-COV-2. In addition, some natural products have displayed activities of immunomodulation, antiinflammatory, and antihepatic failure in COVID-19 clinical trials, which may relate to their non-monomeric structures. However, further evaluation and high-quality assessments, including safety verification tests, drug interaction tests, and clinical trials, are needed to substantiate natural products' multi-target and multi-pathway effects on COVID-19. Here, we review the literature on several promising active natural products that may act as vaccine immune enhancers or provide targeted anti-COVID-19 drugs. The structures, mechanisms of action, and research progress of these natural products are analyzed, to hopefully provide effective ideas for the development of targeted drugs that possess better structure, potency, and safety.

Interacciones farmacológicas entre antivirales y plantas medicinales / Pharmacological interactions between antivirals and medicinal plants

Resumen: Objetivo: Identificar las plantas medicinales que presentan interacciones farmacológicas con los fármacos antivirales. Materiales y métodos: Se realizó una revisión bibliográfica mediante la recolección de artículos en las bases de datos PubMed, Scielo, Google académico. Se recuperó información de cada una de las plantas estudiadas hasta mayo de 2018. Se confeccionó una ficha instructiva a partir de la información obtenida, se tuvo en cuenta su utilidad y actualidad. Resultados: El 57.9% de la información fue recuperada de Google académico. El 47.9% del total de estudios revisados se referían a estudios clínicos y el 27% fueron investigaciones realizadas en Cuba. Allium sativum L. (19.7%), Hypericum perforatum (7.8%) y Panax quinquefolius (7.6%) fueron las plantas que presentaron mayor número de estudios concernientes a interacciones con antivirales. Las acciones sobre el citocromo P450 y la glicoproteína-P fueron las principales responsables de la ocurrencia de interacciones entre las plantas medicinales y los antivirales. La curcumina metabolito secundario de la Curcuma longa L. mostró potencial actividad antiviral ante virus de inmunodeficiencia humana tipo 1 sin obtenerse resultados concluyentes. Conclusiones: Podemos concluir que a pesar de que las interacciones farmacológicas entre antivirales y plantas medicinales son escasas, cuando se presentan lo hacen, en su mayoría, en forma de alteraciones farmacocinéticas. Los antirretrovirales fueron los fármacos de este grupo más involucrados en interacciones con plantas de uso común como el ajo. Los resultados encontrados fueron contradictorios en ocasiones y no todos estaban basados en evidencias clínicas.

Abstract: Objective: To identify medicinal plants that show pharmacological interactions with antiviral drugs. Materials and methods: A literature review carried out through the collection of articles in the PubMed, Scielo, Google academic databases. Information retrieved from each of the plants studied up to May 2018. An information sheet was prepared based on the information obtained and taking into account its usefulness and topicality. Results: 57.9% of the information was retrieved from academic Google. 47.9% of the total studies reviewed referred to clinical studies and 27% were investigations carried out in Cuba. Allium sativum L. (19.7%), Hypericum perforatum (7.8%) and Panax quinquefolius (7.6%) were the plants that presented the highest number of studies concerning interactions with antivirals. Actions on cytochrome P450 and P-glycoprotein were mainly responsible for the occurrence of interactions between medicinal plants and antivirals. The secondary metabolite curcumin of Curcuma longa L. showed potential antiviral activity against human immunodeficiency virus type 1 without obtaining conclusive results. Conclusions: We can conclude that although the interactions between antivirals and medicinal plants are rather rare when they occur, they do so mostly in the form of pharmacokinetic alterations. Antiretroviral drugs are the drugs of this group most involved in interactions with commonly used plants such as garlic. The results found are not all base on clinical evidence and sometime they were contradictories.

Impact of Azithromycin on Forsythiaside Pharmacokinetics in Rats: A Population Modeling Method.

OBJECTIVE: Lianhuaqingwen and Shuanghuanglian are drug treatment options for Corona Virus Disease 2019 (COVID-19). In China, use of traditional Chinese medicine with Shuanghuanglian or Lianhuaqingwen (for them, forsythiaside is the active antiviral and antibacterial component) in combination with azithromycin is common for the treatment of pediatric pneumonia. It is important to understand the reason why the combination of these compounds is better than a single drug treatment. This study aimed to explore the pharmacokinetic interaction between forsythiaside and azithromycin. METHODS: Twelve male Sprague-Dawley rats were randomly divided into an experimental group (Forsythia suspensa extract and azithromycin) and a control group (a single dose of Forsythia suspensa extract in 5% glucose solution). Plasma samples were collected at scheduled time points, and the high-performance liquid chromatography combined with ultraviolet method was used to determine the plasma forsythiaside concentration. Non-compartmental analysis and population pharmacokinetic methods were used to investigate the forsythiaside pharmacokinetic difference between the experimental and control group. RESULTS: Compared with a single administration, the area under the curve and half-life of forsythiaside increased, and forsythiaside clearance decreased significantly after co-administration with azithromycin. The in vivo behavior of forsythiaside could be described by the one compartment model. The forsythiaside clearance decreased when combined with azithromycin. Visual evaluation and bootstrap results suggested that the final model was precise and stable. CONCLUSION: Co-administration of azithromycin can significantly decrease the forsythiaside clearance and increase drug exposure. A lower dose of azithromycin can obtain sufficient forsythiaside concentration to provide antiviral and antibacterial activity.

Hypericum perforatum and Its Ingredients Hypericin and Pseudohypericin Demonstrate an Antiviral Activity against SARS-CoV-2.

For almost two years, the COVID-19 pandemic has constituted a major challenge to human health, particularly due to the lack of efficient antivirals to be used against the virus during routine treatment interventions. Multiple treatment options have been investigated for their potential inhibitory effect on SARS-CoV-2. Natural products, such as plant extracts, may be a promising option, as they have shown an antiviral activity against other viruses in the past. Here, a quantified extract of Hypericum perforatum was tested and found to possess a potent antiviral activity against SARS-CoV-2. The antiviral potency of the extract could be attributed to the naphtodianthrones hypericin and pseudohypericin, in contrast to other tested ingredients of the plant material, which did not show any antiviral activity. Hypericum perforatum and its main active ingredient hypericin were also effective against different SARS-CoV-2 variants (Alpha, Beta, Delta, and Omicron). Concerning its mechanism of action, evidence was obtained that Hypericum perforatum and hypericin may hold a direct virus-blocking effect against SARS-CoV-2 virus particles. Taken together, the presented data clearly emphasize the promising antiviral activity of Hypericum perforatum and its active ingredients against SARS-CoV-2 infections.

Utilization of Aloe Compounds in Combatting Viral Diseases.

Plants contain underutilized resources of compounds that can be employed to combat viral diseases. Aloe vera (L.) Burm. f. (syn. Aloe barbadensis Mill.) has a long history of use in traditional medicine, and A. vera extracts have been reported to possess a huge breadth of pharmacological activities. Here, we discuss the potential of A. vera compounds as antivirals and immunomodulators for the treatment of viral diseases. In particular, we highlight the use of aloe emodin and acemannan as lead compounds that should be considered for further development in the management and prevention of viral diseases. Given the immunomodulatory capacity of A. vera compounds, especially those found in Aloe gel, we also put forward the idea that these compounds should be considered as adjuvants for viral vaccines. Lastly, we present some of the current limitations to the clinical applications of compounds from Aloe, especially from A. vera.

Changes in Serum Interferon Gamma and Interleukin-10 in Relation to Direct-Acting Antiviral Therapy of Chronic Hepatitis C Genotype 4: A Pilot Study.

Introduction: This study analyzes the changing levels of circulating inflammatory cytokines Interferon gamma (IFN-γ) and interleukin (IL)-10 (as the main cytokines of T-helper-1 and T-helper-2 immune responses) in patients with chronic hepatitis C virus (HCV) infection undergoing therapy with direct-acting antivirals (DAAs) and to correlate them with laboratory markers. Methods: This Pilot study included 50 HCV monoinfected patients who received DAAs for 12 or 24 weeks. They were followed up monthly during therapy and 3 months after the end of the treatment. Liver disease was determined by transient elastography, in addition to FIB-4 indices. Analysis of IFN-gamma and IL-10 was carried out using an enzyme-linked immunosorbent assay. Results: All patients carried HCV genotype 4. The Sustained virological response was 100% and 92% in cirrhotics and noncirrhotics, respectively. There was no significant difference between groups in baseline IL-10 or IFN-gamma. In noncirrhotics, IL-10 showed a significant reduction at Week 4 after treatment start. In cirrhotics, IL-10 showed a significant reduction at Week 4 after treatment starts and a significant reduction at Week 12 after the end of the treatment. At Week 12 after the end of the treatment, serum IL-10 levels were significantly lower in cirrhotics. IFN-γ showed nonsignificant changes in noncirrhotics. A significant increase of IFN-γ occurred in cirrhotics from Week 4 after treatment starts to 12 weeks after the end of the treatment. IFN-γ was significantly higher in cirrhotics at Week 12 after the end of the treatment. IFN-γ and IL-10 showed different correlations with laboratory markers. Conclusion: Viral eradication induced by DAAs caused a significant change in IL-10 and IFN-gamma.