Antiviral Research Articles

The Antiretroviral Pregnancy Registry: Three decades of prospective monitoring for birth defects.

Antiretrovirals (ARVs) are life-saving drugs used for the treatment and prevention of HIV infection and antiviral drugs (AVs) for the treatment of chronic HBV infection. ARVs have proven highly effective in reducing perinatal HIV transmission, however the risk of birth defects from prenatal exposure to ARVs/AVs is an ongoing concern. The Antiretroviral Pregnancy Registry (APR), an international, prospective exposure-registration cohort study, monitors ARV and AV use in pregnancy for early signals of teratogenicity. This communication reports results of 30-years' experience of ARV/AV exposure during pregnancy and lessons learned through continuous quality improvement. Birth defect prevalence is estimated and compared to internal and external groups. Statistical inference is based on exact methods for binomial proportions. Between 2006 and 2023, cumulative enrollment more than tripled from 6893 to 25 960 pregnancies and ARVs/AVs monitored increased from 29 to 222. Through January 2023, there were 21 636 live births and 631 outcomes with birth defects, for overall prevalence of 2.9/100 live births (95% CI 2.7, 3.2). The birth defect prevalence was 3.0% (95% CI 2.7%, 3.3%) among first trimester exposures and 2.8% (95% CI 2.5%, 3.2%) among second/third trimester exposures (prevalence ratio 1.04 [95% CI 0.89, 1.21]). Birth defect prevalence is not statistically significantly different between first trimester ARV/AV pregnancy exposures compared to second/third trimester exposures and is also not different from two population-based surveillance systems: 2.72/100 live births reported in the Metropolitan Atlanta Congenital Defects Program (MACDP); and 4.17/100 live births from the Texas Birth Defects Registry (TBDR).

Antiviral Compounds to Address Influenza Pandemics: An Update from 2016-2022.

In recent decades, the world has gained experience of the dangerous effects of pandemic events caused by emerging respiratory viruses. In particular, annual epidemics of influenza are responsible for severe illness and deaths. Even if conventional influenza vaccines represent the most effective tool for preventing virus infections, they are not completely effective in patients with severe chronic disease and immunocompromised and new small molecules have emerged to prevent and control the influenza viruses. Thus, the attention of chemists is continuously focused on the synthesis of new antiviral drugs able to interact with the different molecular targets involved in the virus replication cycle. To date, different classes of influenza viruses inhibitors able to target neuraminidase enzyme, hemagglutinin protein, Matrix-2 (M2) protein ion channel, nucleoprotein or RNA-dependent RNA polymerase have been synthesized using several synthetic strategies comprising the chemical modification of currently used drugs. The best results, in terms of inhibitory activity, are in the nanomolar range and have been obtained from the chemical modification of clinically used drugs such as Peramivir, Zanamivir, Oseltamir, Rimantadine, as well as sialylated molecules, and hydroxypyridinone derivatives. The aim of this review is to report, covering the period 2016-2022, the most recent routes related to the synthesis of effective influenza virus inhibitors.

Synthesis of Novel Fluoro Phenyl Triazoles Via Click Chemistry with or without Microwave Irradiation and their Evaluation as Anti-proliferative Agents in SiHa Cells.

Perform the synthesis of novel fluoro phenyl triazoles via click chemistry with or without microwave irradiation and their evaluation as anti-proliferative agents in SiHa cells. Triazoles are heterocyclic compounds containing a five-member ring with two carbon and three nitrogen atoms. They are of great importance since many of them have shown to have biological activity as antifungal, antiviral, antibacterial, anti-HIV, anti-tuberculosis, vasodilator, and anticancer agents. Synthesize novel fluoro phenyl triazoles via click chemistry and evaluate their antiproliferative activity. First, several fluorophenyl azides were prepared. Reacting these aryl azides with phenylacetylene in the presence of Cu(I) catalyst, the corresponding fluoro phenyl triazoles were obtained by two methodologies, stirring at room temperature and under microwave irradiation at 40ºC. In addition, their antiproliferative activity was evaluated in cervical cancer SiHa cells. Fluoro phenyl triazoles were obtained within minutes by means of microwave irradiation. The compound 3f, containing two fluorine atoms next to the carbon connected to the triazole ring, was the most potent among the fluoro phenyl triazoles tested in this study. Interestingly, the addition of a fluorine atom to the phenyl triazole structure in a specific site increases its antiproliferative effect as compared to parent phenyl triazole 3a without a fluorine atom. Several fluoro phenyl triazoles were obtained by reacting fluoro phenyl azides with phenylacetylene in the presence of copper sulphate, sodium ascorbate and phenanthroline. Preparation of these triazoles with MW irradiation represents a better methodology since they are obtained within minutes and higher yields of cleaner compounds are obtained. In terms of biological studies, the proximity between fluorine atom and triazole ring increases its biological activity.

Monkeypox Virus (MPXV) Infection: A Review.

Monkeypox is a viral disease; its outbreak was recently declared a global emergency by the World Health Organization. For the first time, a monkeypox virus (MPXV)-infected patient was found in India. Various researchers back-to-back tried to find the solution to this health emergency just after COVID-19. In this review, we discuss the current outbreak status of India, its transmission, virulence factors, symptoms, treatment, and the preventive guidelines generated by the Indian Health Ministry. We found that monkeypox virus (MPXV) disease is different from smallpox, and the age group between 30-40 years old is more prone to MPXV disease. We also found that, besides homosexuals, gays, bisexuals, and non-vegetarians, it also affects normal straight men and women who have no history of travel. Close contact should be avoided from rats, monkeys and sick people who are affected by monkeypox. To date, there are no monkeypox drugs, but Tecovirimat is more effective than other drugs that are used for other viral diseases like smallpox. Therefore, we need to develop an effective antiviral agent against the virulence factor of MXPV.

Development of Pomegranate Aloe Vera Juice: Pomalo

Abstract: Pomegranate juice is a good source of polyphenols and has good antioxidant potential, whereas, the studies on pomegranate juice have shown that it possesses antiatherogenic, antioxidant, antihypertensive, and anti-inflammatory properties. The literature also reported the major decrease in atherosclerotic lesion region in immune-deficient mice and intima media thickness in cardiac patients on medications, due to consumption of pomegranate juice. Whereas, in patients with type 2 diabetes, a reduction in lipid peroxidation was observed and in hypertensive patients, a systolic blood pressure and serum angiotensin converting enzyme activity was determined. Therefore, the study showed the potential cardioprotective advantages of pomegranate juice and suggests the inclusion of this juice in a diet for a healthy living. the composition of aloe vera and its role in development of functional foods. The colorless and watery gel-like consistency are the characteristics of aloe vera gel that makes it better option for blend beverages. The functional characteristics render aloe vera with broad range of application in the pharmaceutical, cosmetics and food sectors. The presence of antioxidants and hormones (auxins and gibberellins) in aloe vera, are responsible for preventing chronic diseases and wound healing properties by inducing the cell propagation, thus providing anti-inflammatory action, respectively. Saponins and salicylic acid present in it, provides antibacterial and antiseptic activity. The literature also reveals that emidine and aloin are the compounds present in aloe that act as antiviral, antibacterial and analgesic agent. Whereas, it also contains vitamins E, C and minerals such as, copper, selenium and zinc, along with enzyme brady kinase, fatty acids and sugar, essential and non-essential amino acids, 12 anthraquinones phenolic compounds. The most abundant monosaccharide and polysaccharides found in aloe vera are Mannose-6-phosphate, and glucomannans, respectively.

Hexestrol, an estrogen receptor agonist, inhibits Lassa virus entry.

Lassa virus (LASV) is the causative agent of human Lassa fever which in severe cases manifests as hemorrhagic fever leading to thousands of deaths annually. However, no approved vaccines or antiviral drugs are currently available. Recently, we screened approximately 2,500 compounds using a recombinant vesicular stomatitis virus (VSV) expressing LASV glycoprotein GP (VSV-LASVGP) and identified a P-glycoprotein inhibitor as a potential LASV entry inhibitor. Here, we show that another identified candidate, hexestrol (HES), an estrogen receptor agonist, is also a LASV entry inhibitor. HES inhibited VSV-LASVGP replication with a 50% inhibitory concentration (IC50) of 0.63 µM. Importantly, HES also inhibited authentic LASV replication with IC50 values of 0.31 µM-0.61 µM. Time-of-addition and cell-based membrane fusion assays suggested that HES inhibits the membrane fusion step during virus entry. Alternative estrogen receptor agonists did not inhibit VSV-LASVGP replication, suggesting that the estrogen receptor itself is unlikely to be involved in the antiviral activity of HES. Generation of a HES-resistant mutant revealed that the phenylalanine at amino acid position 446 (F446) of LASVGP, which is located in the transmembrane region, conferred resistance to HES. Although mutation of F446 enhanced the membrane fusion activity of LASVGP, it exhibited reduced VSV-LASVGP replication, most likely due to the instability of the pre-fusion state of LASVGP. Collectively, our results demonstrated that HES is a promising anti-LASV drug that acts by inhibiting the membrane fusion step of LASV entry. This study also highlights the importance of the LASVGP transmembrane region as a target for anti-LASV drugs.IMPORTANCELassa virus (LASV), the causative agent of Lassa fever, is the most devastating mammarenavirus with respect to its impact on public health in West Africa. However, no approved antiviral drugs or vaccines are currently available. Here, we identified hexestrol (HES), an estrogen receptor agonist, as the potential antiviral candidate drug. We showed that the estrogen receptor itself is not involved in the antiviral activity. HES directly bound to LASVGP and blocked membrane fusion, thereby inhibiting LASV infection. Through the generation of a HES-resistant virus, we found that phenylalanine at position 446 (F446) within the LASVGP transmembrane region plays a crucial role in the antiviral activity of HES. The mutation at F446 caused reduced virus replication, likely due to the instability of the pre-fusion state of LASVGP. These findings highlight the potential of HES as a promising candidate for the development of antiviral compounds targeting LASV.

Antiviral therapies for the management of persistent coronavirus disease 2019 in immunocompromised hosts: A narrative review.

Antiviral agents with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have played a critical role in disease management; however, little is known regarding the efficacy of these medications in the treatment of SARS-CoV-2 infection in immunocompromised patients, particularly in the management of persistent SARS-CoV-2 positivity. This narrative review discusses the management of persistent coronavirus disease 2019 in immunocompromised hosts, with a focus on antiviral therapies. We identified 84 cases from the literature describing a variety of approaches, including prolonged antiviral therapy (n = 11), combination antivirals (n = 13), and mixed therapy with antiviral and antibody treatments (n = 60). A high proportion had an underlying haematologic malignancy (n = 67, 80%), and were in receipt of anti-CD20 agents (n = 51, 60%). Success was reported in 70 cases (83%) which varied according to the therapy type. Combination therapies with antivirals may be an effective approach for individuals with persistent SARS-CoV-2 positivity, particularly those that incorporate treatments aimed at increasing neutralizing antibody levels. Any novel approaches taken to this difficult management dilemma should be mindful of the emergence of antiviral resistance.

Desymmetric Hydrogenation of meso-Dicarboxylic Acids.

Efficient transformation of platform chemicals into key intermediates has been increasingly important for the pharmaceutical industry. The development of the catalytic reduction of abundant carboxylic acids with molecular hydrogen has been of both practical and theoretical value. We herein report the homogeneous hydrogenation of dicarboxylic acids with the strategy of desymmetrization. Using a rhodium/bisphosphine catalyst, one carboxyl group of meso-diacids was selectively reduced to yield chiral lactones with satisfactory enantioselectivity. This method provides a straightforward approach to produce chiral lactone intermediates for the manufacture of biotin, telaprevir, and other antivirus drugs. Both experimental and computational investigations were carried out, revealing a novel neighboring group coordination mechanism in the catalytic cycle.

Dynamics of the Herpes simplex virus DNA polymerase holoenzyme during DNA synthesis and proof-reading revealed by Cryo-EM.

Herpes simplex virus 1 (HSV-1), a double-stranded DNA virus, replicates using seven essential proteins encoded by its genome. Among these, the UL30 DNA polymerase, complexed with the UL42 processivity factor, orchestrates leading and lagging strand replication of the 152 kb viral genome. UL30 polymerase is a prime target for antiviral therapy, and resistance to current drugs can arise in immunocompromised individuals. Using electron cryo-microscopy (cryo-EM), we unveil the dynamic changes of the UL30/UL42 complex with DNA in three distinct states. First, a pre-translocation state with an open fingers domain ready for nucleotide incorporation. Second, a halted elongation state where the fingers close, trapping dATP in the dNTP pocket. Third, a DNA-editing state involving significant conformational changes to allow DNA realignment for exonuclease activity. Additionally, the flexible UL30 C-terminal domain interacts with UL42, forming an extended positively charged surface binding to DNA, thereby enhancing processive synthesis. These findings highlight substantial structural shifts in the polymerase and its DNA interactions during replication, offering insights for future antiviral drug development.

Zafirlukast, as a viral inactivator, potently inhibits infection of several flaviviruses, including Zika virus, dengue virus, and yellow fever virus.

Zika virus (ZIKV) is one of the mosquito-borne flaviviruses that exhibits a unique tropism to nervous systems and is associated with Guillain-Barre syndrome and congenital Zika syndrome (CZS). Dengue virus (DENV) and yellow fever virus (YFV), the other two mosquito-borne flaviviruses, have also been circulating for a long time and cause severe diseases, such as dengue hemorrhagic fever and yellow fever, respectively. However, there are no safe and effective antiviral drugs approved for the treatment of infections or coinfections of these flaviviruses. Here, we found that zafirlukast, a pregnancy-safe leukotriene receptor antagonist, exhibited potent antiviral activity against infections of ZIKV strains from different lineages in different cell lines, as well as against infections of DENV-2 and YFV 17D. Mechanistic studies demonstrated that zafirlukast directly and irreversibly inactivated these flaviviruses by disrupting the integrity of the virions, leading to the loss of viral infectivity, hence inhibiting the entry step of virus infection. Considering its efficacy against flaviviruses, its safety for pregnant women, and its neuroprotective effect, zafirlukast is a promising candidate for prophylaxis and treatment of infections or coinfections of ZIKV, DENV, and YFV, even in pregnant women.

Recent Developments in Antimicrobial and Antiviral Agents Based on Natural/Synthetic Polymers and Dendrimers: Design and Therapeutic Applications

AbstractThis review article explores the recent innovations in the field of antimicrobial and antiviral macromolecules. With the rising challenge of antibiotic resistance, as well as the overuse of antibiotics, there is a growing demand for efficient solutions to combat microbial and viral infections. The development of new effective antimicrobial and antiviral agents is highlighted. This review was designed to give a comprehensive view of the literature focusing on a few examples of combating microbial and viral infections in each section. A brief description of naturally occurring organic‐based materials that exhibited antimicrobial and/or antiviral activities is presented, focusing on polysaccharides, peptides and proteins. Synthetic organic‐based materials are divided into subsections including polymers, dendrimers, and nanomaterials. The synthesis and applications of inorganic materials such as polyphosphazenes and polysiloxanes, as well as tin‐, germanium‐ and gallium‐based materials are emphasized in this review. Organometallic macromolecules are also described, and their antimicrobial and antiviral activities are examined. Overall, this article provides a comprehensive overview of recent advancements in the design of antimicrobial and antiviral macromolecules, offering valuable insights into their potential applications in biomedical research and combating drug‐resistant microorganisms and viruses.This article is protected by copyright. All rights reserved

Effectiveness of test-and-treat model with direct-acting antiviral for hepatitis C virus infection in migrants: a prospective interventional study in Italy.

Migrants, mainly undocumented and low-income refugees, are at high risk of hepatitis C virus (HCV) infection, but are a difficult-to-reach and to-treat population. The aim of the study was to evaluate the effectiveness of a test and treat model with direct-acting antiviral for HCV infection in these migrants coming from low-income and living in southern Italy. A prospective, multicenter, collaborative study based on a four-phase-program (educational counseling, screening, linkage-to-care and treatment) was designed in southern Italy; the study started in June 2018, was stopped in February 2020 because of the outbreak of SARS-CoV2 infection in Italy and was resumed in February 2021 until November 2021. After educational counseling on infectious diseases that are transmitted through blood or sexually pseudonymized HCV screening was offered to all undocumented migrants and low-income refugees observed at one of the 1st level clinical centers. The HCV-RNA-positive subjects were referred to one of the 3rd level units of Infectious Diseases (ID) and treated with a 12-week course of sofosbuvir-velpatasvir and observed for 12 weeks after the end of direct antiviral agents (DAA) treatment. For the descriptive analysis, the categorical variables were reported as absolute numbers and relative frequencies. Continuous variables were summarized as mean and standard deviation (SD) if normally distributed, or as a median and interquartile range (IQR) if not normally distributed. We used Pearson chi-square or Fisher's exact test for categorical variables and Student's t test or Mann-Whitney test for continuous variables. A P value < 0.05 was considered to be statistically significant. Analyses were performed with SPSS 21.0. Of the 3501migrants observed in the study period, 3417 (97.6%) agreed to be screened; 185 (4.7%) were anti-HCV-positive and, of these, 53 (28.6%) were HCV-RNA-positive. Of these 53 subjects, 48 (90.5%) were referred to an ID unit and started DAA treatment. The HCV-RNA-positive-subjects were older [median 36 years (IQR: 32-21) vs 27.19 (IQR: 30.5-19.25); P = 0.001], and less frequently males [35 (66.03 %) vs 119 (90.1%), P < 0 .0001] than seronegative participants. They more frequently came from Eastern Europe (70.8%) stayed longer in Italy [months of stay in Italy, mean ± SD: 51.02±52.84 vs 25.7 ± 42.65, P = 0.001], and had more years of schooling [years of schooling, mean ± SD: 9.61±2.81 vs 7.10 ± 4, P = 0.0001]. HCV-RNA-positive-subjects less frequently reported piercing, tattoos and tribal scars as risk factors (23.6%). Of these 48 HCV RNA positive subjects who started DAA, 47 (97.9%) showed a sustained virological response and one dropped-out in follow-up after DAA treatment. No subject had any adverse event. This model of HCV screening and linkage to care seems effective to eliminate HCV infectionin a difficult-to-reach and to-treat population, such as undocumented migrants and low-income refugees. The participation of cultural mediators in the study made possible a better interaction between migrants and physicians, as is evident from the large number of subjects enrolled. Eliminating HCV among migrants will have a long-term positive impact from a public health and healthcare perspective by reducing the number of individuals who potentially develop HCV-related complications such as liver cirrhosis and hepatocellular carcinoma and reducing the circulation of HCV in the regions that host them which often, as in the case of Italy, are low endemic for HCV infection.

Hesperidin, a Potential Antiviral Agent against SARS-CoV-2: The Influence of Citrus Consumption on COVID-19 Incidence and Severity in China

This review examines hesperidin, a citrus bioflavonoid, as a potential antiviral agent against SARS-CoV-2. The COVID-19 pandemic has demanded an urgent need to search for effective antiviral compounds, including those of natural origin, such as hesperidin. The review provides a comprehensive analysis of the chemical properties, bioavailability and antiviral mechanisms of hesperidin, particularly its potential efficacy against SARS-CoV-2. A review of databases, including PubMedPico, Scopus and Web of Science, was conducted using specific keywords and search criteria in accordance with PRISMA (Re-porting Items for Systematic Reviews and Meta-Analysis) guidelines between 2020 and 2024. Of the 207 articles, 37 were selected for the review. A key aspect is the correlation of in vitro, in silico and clinical studies on the antiviral effects of hesperidin with epidemiological data on citrus consumption in China during 2020–2024. The importance of integrating laboratory findings with actual consumption patterns to better understand the role of hesperidin in mitigating COVID-19 was highlighted, and an attempt was made to analyze epidemiological studies to examine the association between citrus juice consumption as a source of hesperidin and the incidence and severity of COVID-19 using China as an example. The review identifies consistencies and discrepancies between experimental and epidemiological data, highlighting the need to correlate the two fields to better understand the potential of hesperidin as an agent against SARS-CoV-2. Challenges and limitations in interpreting the results and future research perspectives in this area are discussed. The aim of this comprehensive review is to bridge the gap between experimental studies and epidemiological evidence and to contribute to the understanding of their correlation.

Antiviral Potential of Fucoxanthin, an Edible Carotenoid Purified from Sargassum siliquastrum, against Zika Virus

Considering the lack of antiviral drugs worldwide, we investigated the antiviral potential of fucoxanthin, an edible carotenoid purified from Sargassum siliquastrum, against zika virus (ZIKV) infection. The antiviral activity of fucoxanthin was assessed in ZIKV-infected Vero E6 cells, and the relevant structural characteristics were confirmed using molecular docking and molecular dynamics (MD) simulation. Fucoxanthin decreased the infectious viral particles and nonstructural protein (NS)1 mRNA expression levels at concentrations of 12.5, 25, and 50 µM in ZIKV-infected cells. Fucoxanthin also decreased the increased mRNA levels of interferon-induced proteins with tetratricopeptide repeat 1 and 2 in ZIKV-infected cells. Molecular docking simulations revealed that fucoxanthin binds to three main ZIKV proteins, including the envelope protein, NS3, and RNA-dependent RNA polymerase (RdRp), with binding energies of −151.449, −303.478, and −290.919 kcal/mol, respectively. The complex of fucoxanthin with RdRp was more stable than RdRp protein alone based on MD simulation. Further, fucoxanthin bonded to the three proteins via repeated formation and disappearance of hydrogen bonds. Overall, fucoxanthin exerts antiviral potential against ZIKV by affecting its three main proteins in a concentration-dependent manner. Thus, fucoxanthin isolated from S. siliquastrum is a potential candidate for treating zika virus infections.

Effects and mechanism of Qingke Pingchuan granules against influenza virus infection.

Qingke Pingchuan granules (QPGs), which contain Houttuynia cordata Thunb, Fritillaria cirrhosa, fired licorice, and fired bitter almonds, among other components, can clear heat and ventilate the lungs, relieving cough and asthma. Clinically, QPGs are mainly used to treat cough, asthma, fever and other discomforts caused by acute or chronic bronchitis. In this study, the antiviral activity of QPGs against respiratory syncytial virus (RSV), influenza A virus A/FM/1/47 (H1N1), oseltamivir-resistant H1N1, A/Beijing/32/92 (H3N2), Sendai virus, and human adenovirus type 3 in Hep-2 or MDCK cells was evaluated using the CCK-8 method, and the cytotoxicity of QPGs to these two cell lines was tested. The effect of QPGs on mice infected with influenza A virus A/FM/1/47 (H1N1) was evaluated by measuring body weight, survival time, and survival rate, as well as virus titers and lesions in the lungs and levels of inflammatory factors in serum. In addition, the expression of TLR-7-My88-NF-κB signaling pathway-related proteins in lung tissues was analyzed by Western blotting and qRT-PCR. The results showed that QPGs had a potent inhibitory effect on the six viruses tested in vitro. Interestingly, QPGs also displayed particularly pronounced antiviral activity against H1N1-OC, similar to that of oseltamivir, a well-known antiviral drug. QPGs effectively protected mice from infection by H1N1, as indicated by significantly increased body weights, survival times, and survival rates and reduced lung virus titers of inflammatory factors and lung tissue injury. The levels of TLR-7-MyD88-NF-κB-pathway-related proteins in the lung tissue of infected mice were found to be decreased after QPG treatment, thereby alleviating lung injury caused by excessive release of inflammatory factors. Taken together, these findings indicate that QPGs have satisfactory activity against influenza virus infection.

Expert consensus on the clinical application of oral small-molecule antiviral drugs against COVID-19

Although COVID-19 no longer constitutes a "public health emergency of international concern", which still has being spreading around the world at a low level. Small molecule drugs are the main antiviral treatment for novel coronavirus recommended in China. Although a variety of small-molecule antiviral drugs against COVID-19 have been listed in China, there is no specific drug recommendation for special populations. Society of Bacterial Infection and Resistance of Chinese Medical Association, together with the National Clinical Research Center for Respiratory Disease, and the National Center for Respiratory Medicine, organized domestic experts in various fields such as respiratory, virology, infection, critical care, emergency medicine and pharmacy to release Expert Consensus on the Clinical Application of Oral Small-Molecule Antiviral Drugs against COVID-19. The main content of this consensus includes the introduction of seven small-molecule antiviral drugs against COVID-19, focusing on the drug recommendations for 14 special groups such as the elderly, patients with complicated chronic diseases, tumor patients, pregnant women, and children, and providing suggestions for clinicians to standardize drug use.

Antiviral Use in Mild-to-Moderate SARS-CoV-2 Infections during the Omicron Wave in Geriatric Patients

(1) Background: Geriatric patients are at high risk of complications of Coronavirus disease-2019 (COVID-19) and are good candidates for antiviral drugs. (2) Methods: A retrospective study of electronic health records (EHRs) aiming to describe antiviral (nirmatrelvir and ritonavir (nirmatrelvir/r) or remdesivir) use, drug–drug interactions (DDIs) and adverse drug reactions (ADRs) in elderly patients (75 and over), hospitalized with mild-to-moderate COVID-19 between July 2022 and June 2023. (3) Results: Out of 491 patients (mean age: 86.9 years), 180 (36.7%) received nirmatrelvir/r, 78 (15.9%) received remdesivir, and 233 (47.4%) received no antiviral therapy. No association was found between the choice of antiviral and the demographic or medical data. No serious ADR was observed. Nirmatrelvir/r dosage adjustment was inadequate in 65% of patients with renal impairment. In total, 128 patients (71%) on nirmatrelvir/r had potential pharmacokinetic DDIs, with 43 resulting in a possibly related ADR. In the remdesivir group, pharmacodynamic DDIs were more frequent, with QTc prolongation risk in 56 patients (72%). Only 20 patients underwent follow-up ECG, revealing QTc prolongation in 4. (4) Conclusions: There is an underutilization of antivirals despite their justified indications. Nirmatrelvir/r dosage was rarely adjusted to renal function. Dose adjustments and closer monitoring are needed due to the high risk of drug interactions.

Spirulina Unveiled: A Comprehensive Review on Biotechnological Innovations, Nutritional Proficiency, and Clinical Implications.

This comprehensive review of Spirulina encompasses biotechnology, phycocyanin production, and purification. Bioactive compounds and vital nutrients are investigated during the study. The literature examines the potential therapeutic advantages and clinical applications of Spirulina. This analysis assesses Spirulina consumption and its associated health risks. The current review offers a comprehensive synthesis of the therapeutic applications as well as technologies utilized for the extraction and purification of phycocyanin. Moreover, this discourse delves into the examination of various advantageous techniques for extracting and purifying phycocyanin, encompassing physical, chemical, and enzymatic methods. The data derived from a multitude of studies strongly indicate the potential therapeutic applications of phycocyanin, encompassing its notable attributes as an antioxidant, anti-inflammatory agent, anticancer agent, antiviral agent, antimicrobial agent, antiallergic agent, anti-obesity agent, antihypertensive agent, and an immunological agent.

Harmol used for the treatment of herpes simplex virus induced keratitis.

Herpes simplex virus type 1 (HSV-1) infection of the eyes results in herpes simplex keratitis (HSK), which has led to vision loss and even blindness in patients. However, the rate of drug resistance in HSV is on the rise; therefore, new antiviral agents with sufficient safety profiles must be developed. At present, we assessed the anti-HSV-1 activity of 502 natural compounds and their ability to reduce the HSV-1-induced cytopathic effect. We chose harmol for further studies because it exhibited the highest antiviral activity. We found that harmol inhibited both HSV-1F and HSV-1/153 (a clinical drug-resistant strain) replication, with an EC50 of 9.34 µM and 5.84 µM, respectively. Moreover, harmol reduced HSV-1 replication in corneal tissues and viral progeny production in tears, and also alleviated early corneal surface lesions related to HSK. For example, harmol treatment preserved corneal thickness and nerve density in HSK mice. Interestingly, harmol also showed a promising antiviral effect on HSV-1/153 induced HSK in mouse model. Furthermore, harmol combined with acyclovir (ACV) treatment showed a greater antiviral effect than either one alone in vitro. Therefore, harmol may be a promising therapeutic agent for managing HSK.

Antiviral Activity of Physta®, Standardised Water Extract of Eurycoma longifolia against SARS-CoV-2: An in vitro Study

Eurycoma longifolia Jack (Simaroubaceae) root extract is known to exhibit antiinflammatory, antiviral and immunomodulatory activities. Therefore, E. longifolia, through a multimodal approach could potentially be used in COVID-19 management. However, to date there has been no investigation into the antiviral activity of E. longifolia root extract against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The objective of the study is to investigate the antiviral activity of Physta® (a standardised water extract of E. longifolia) against SARS-CoV-2. A mitochondrial metabolic activity assay using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) was used to determine the cytotoxicity of the Physta® extract in Vero cells, with concentrations ranging from 1.95 µg/mL to 1,000 µg/mL. Physta® was tested for antiviral activity at six different concentrations, ranging from 3.12 µg/mL to 50 µg/mL. The half maximal cytotoxic concentration (CC50) value of Physta® against Vero cells was estimated at 1,117 µg/mL and the maximum non-toxic dose (MNTD) value was estimated at 60 µg/mL. Physta® inhibited SARS-CoV-2 replication in a dose-dependent manner, and the half maximal inhibition concentration (IC50) was estimated to be 36.3 µg/mL. This study has demonstrated the antiviral activity of Physta® against SARS-CoV-2. Future evaluations in animal and clinical settings should be conducted to determine whether Physta® can be used alone or in combination with other antiviral agents to alleviate COVID-19.