Molecular Characterization of Bacterial Isolates from Soil Samples and Evaluation of their Antibacterial Potential against MDRS

Some soil microbes, with their diverse inhabitance, biologically active metabolites, and endospore formation, gave them characteristic predominance and recognition among other microbial communities. The present study collected ten soil samples from green land, agricultural and marshy soil sites of Khyber Pakhtunkhwa, Pakistan. After culturing on described media, the bacterial isolates were identified through phenotypic, biochemical and phylogenetic analysis. Our phylogenetic analysis revealed three bacterial isolates, A6S7, A1S6, and A1S10, showing 99% nucleotides sequence similarity with Brevibacillus formosus, Bacillus Subtilis and Paenibacillus dendritiformis. The crude extract was prepared from bacterial isolates to assess the anti-bacterial potential against various targeted multidrug-resistant strains (MDRS), including Acinetobacter baumannii (ATCC 19606), Methicillin-resistant Staphylococcus aureus (MRSA) (BAA-1683), Klebsiella pneumoniae (ATCC 13883), Pseudomonas aeruginosa (BAA-2108), Staphylococcus aureus (ATCC 292013), Escherichia coli (ATCC25922) and Salmonella typhi (ATCC 14028). Our analysis revealed that all bacterial extracts possess activity against Gram-negative and Gram-positive bacteria at a concentration of 5 mg/mL, efficiently restricting the growth of E. coli compared with positive control ciprofloxacin. The study concluded that the identified species have the potential to produce antimicrobial compounds which can be used to control different microbial infections, especially MDRS. Moreover, the analysis of the bacterial extracts through GC-MS indicated the presence of different antimicrobial compounds such as propanoic acid, oxalic acid, phenol and hexadecanoic acid.     

Antiviral Effects of Green Tea EGCG and Its Potential Application against COVID-19

(–)-Epigallocatechin-3-O-gallate (EGCG), the most abundant component of catechins in tea (Camellia sinensis (L.) O. Kuntze), plays a role against viruses through inhibiting virus invasiveness, restraining gene expression and replication. In this paper, the antiviral effects of EGCG on various viruses, including DNA virus, RNA virus, coronavirus, enterovirus and arbovirus, were reviewed. Meanwhile, the antiviral effects of the EGCG epi-isomer counterpart (+)-gallocatechin-3-O-gallate (GCG) were also discussed.     

Antiviral Activities of Officinaloside C against Herpes Simplex Virus-1

The iridoid compounds in traditional Chinese medicine play a prominent role in their antiviral effects. We previously reported the anti-inflammatory effect of new iridoids from the aerial parts of Morinda officinalis. Nevertheless, several open questions remain to explore the other biological functions of these new iridoid compounds. Herpes simplex virus-1 (HSV-1) is one of the most prevalent pathogens in human beings worldwide and due to limited therapies, mainly with the guanosine analog aciclovir (ACV) and other analogs, the search for new drugs with different modes of action and low toxicity becomes particularly urgent for public health. This study aimed to explore the anti-HSV-1 effects of iridoids from the aerial parts of Morinda officinalis. The dried aerial parts of Morinda officinalis were extracted with 95% ethanol and systematic separation and purification were then carried out by modern column chromatography methods such as silica gel column, RP-ODS column, Sephadex LH-20 gel column, and semi-preparative liquid phase, and the structure of these compounds were identified through the physical and chemical properties and a variety of spectral techniques. The obtained seven new iridoid compounds were screened for antiviral activity on HSV-1 through CCK8 and the cytopathic effect, and then the plaque reduction assay, the anti-fluorescence reporter virus strain replication, and RT-qPCR experiments were carried out to further evaluate the antiviral effect. Seven new iridoid compounds (officinaloside A–G) were identified from the aerial parts of Morinda officinalis, and officinaloside C showed anti-HSV-1 activity. Further functional experiments confirmed that officinaloside C has a significant inhibiting effect on HSV-1 virus plaque formation, viral gene, and protein expression, and fluorescent virus replication. Our findings suggest that officinaloside C has significant inhibitory effects on viral plaque formation, genome replication, and viral protein expression of HSV-1 which implies that officinaloside C exhibits viral activity and may be a promising treatment for HSV-1 infection.     

Synthesis and Antiviral Properties against SARS-CoV-2 of Epoxybenzooxocino[4,3-b]Pyridine Derivatives

The COVID-19 pandemic is ongoing as of mid-2022 and requires the development of new therapeutic drugs, because the existing clinically approved drugs are limited. In this work, seven derivatives of epoxybenzooxocinopyridine were synthesized and tested for the ability to inhibit the replication of the SARS-CoV-2 virus in cell cultures. Among the described compounds, six were not able to suppress the SARS-CoV-2 virus’ replication. One compound, which is a derivative of epoxybenzooxocinopyridine with an attached side group of 3,4-dihydroquinoxalin-2-one, demonstrated antiviral activity comparable to that of one pharmaceutical drug. The described compound is a prospective lead substance, because the half-maximal effective concentration is 2.23 μg/μL, which is within a pharmacologically achievable range.     

Antiviral Therapeutic Potential of Curcumin: An Update

The treatment of viral disease has become a medical challenge because of the increasing incidence and prevalence of human viral pathogens, as well as the lack of viable treatment alternatives, including plant-derived strategies. This review attempts to investigate the trends of research on in vitro antiviral effects of curcumin against different classes of human viral pathogens worldwide. Various electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar were searched for published English articles evaluating the anti-viral activity of curcumin. Data were then extracted and analyzed. The forty-three studies (published from 1993 to 2020) that were identified contain data for 24 different viruses. The 50% cytotoxic concentration (CC50), 50% effective/inhibitory concentration (EC50/IC50), and stimulation index (SI) parameters showed that curcumin had antiviral activity against viruses causing diseases in humans. Data presented in this review highlight the potential antiviral applications of curcumin and open new avenues for further experiments on the clinical applications of curcumin and its derivatives.     

Potential Antiviral Action of Alkaloids

Viral infections and outbreaks have become a major concern and are one of the main causes of morbidity and mortality worldwide. The development of successful antiviral therapeutics and vaccines remains a daunting challenge. The discovery of novel antiviral agents is a public health emergency, and extraordinary efforts are underway globally to identify safe and effective treatments for different viral diseases. Alkaloids are natural phytochemicals known for their biological activities, many of which have been intensively studied for their broad-spectrum of antiviral activities against different DNA and RNA viruses. The purpose of this review was to summarize the evidence supporting the efficacy of the antiviral activity of plant alkaloids at half-maximum effective concentration (EC₅₀) or half-maximum inhibitory concentration (IC₅₀) below 10 μM and describe the molecular sites most often targeted by natural alkaloids acting against different virus families. This review highlights that considering the devastating effects of virus pandemics on humans, plants, and animals, the development of high efficiency and low-toxicity antiviral drugs targeting these viruses need to be developed. Furthermore, it summarizes the current research status of alkaloids as the source of antiviral drug development, their structural characteristics, and antiviral targets. Overall, the influence of alkaloids at the molecular level suggests a high degree of specificity which means they could serve as potent and safe antiviral agents waiting for evaluation and exploitation.     

Antiviral Effect of Bovine Lactoferrin against Enterovirus E

Enterovirus E (EV-E), a representative of the Picornaviridae family, endemically affects cattle across the world, typically causing subclinical infections. However, under favorable conditions, severe or fatal disorders of the respiratory, digestive, and reproductive systems may develop. There is no specific treatment for enterovirus infections in humans or animals, and only symptomatic treatment is available. The aim of this study was to determine the in vitro antiviral effect of bovine lactoferrin (bLF) against enterovirus E using virucidal, cytopathic effect inhibition, and viral yield reduction assays in MDBK cells. The influence of lactoferrin on the intracellular viral RNA level was also determined. Surprisingly, lactoferrin did not have a protective effect on cells, although it inhibited the replication of the virus during the adsorption and post-adsorption stages (viral titres reduced by 1–1.1 log). Additionally, a decrease in the viral RNA level in cells (by up to 75%) was observed. More detailed studies are needed to determine the mechanism of bovine lactoferrin effect on enterovirus E. However, this highly biocompatible protein ensures some degree of protection against infection by bovine enterovirus, which is particularly important for young animals that receive this protein in their mother’s milk.     

Green Synthesized Zinc Oxide Nanoparticles Based on Cestrum diurnum L. of Potential Antiviral Activity against Human Corona 229-E Virus

SARS-CoV-2 has caused more than 596 million infections and 6 million fatalities globally. Looking for urgent medication for prevention, treatment, and rehabilitation is obligatory. Plant extracts and green synthesized nanoparticles have numerous biological activities, including antiviral activity. HPLC analysis of C. dirnum L. leaf extract showed that catechin, ferulic acid, chlorogenic acid, and syringic acid were the most major compounds, with concentrations of 1425.16, 1004.68, 207.46, and 158.95 µg/g, respectively. Zinc nanoparticles were biosynthesized using zinc acetate and C. dirnum extract. TEM analysis revealed that the particle size of ZnO-NPs varied between 3.406 and 4.857 nm. An XRD study showed the existence of hexagonal crystals of ZnO-NPs with an average size of 12.11 nm. Both ZnO-NPs (IC₅₀ = 7.01 and CC₅₀ = 145.77) and C. dirnum L. extract (IC₅₀ = 61.15 and CC₅₀ = 145.87 µg/mL) showed antiviral activity against HCOV-229E, but their combination (IC₅₀ = 2.41 and CC₅₀ = 179.23) showed higher activity than both. Molecular docking was used to investigate the affinity of some metabolites against the HCOV-229E main protease. Chlorogenic acid, solanidine, and catchin showed high affinity (−7.13, −6.95, and −6.52), compared to the ligand MDP (−5.66 Kcal/mol). Cestrum dinurum extract and ZnO-NPs combination should be subjected to further studies to be used as an antiviral drug.     

Antiviral activity of aconite alkaloids from Aconitum carmichaelii Debx

Four diterpenoid alkaloids, namely, (a) hypaconitine, (b) songorine, (c) mesaconitine and (d) aconitine, were isolated from the ethanol root extract of Aconitum carmichaelii Debx. The antiviral activities of these alkaloids against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) were evaluated. Antiviral activity test in vivo showed that compounds a and c, which were C19-diterpenoid alkaloids, showed inactivation efficacy values of 82.4 and 85.6% against TMV at 500 μg/mL, respectively. By contrast, compound c presented inactivation activity of 52.1% against CMV at 500 μg/mL, which was almost equal to that of the commercial Ningnanmycin (87.1% inactivation activity against TMV and 53.8% inactivation activity against CMV). C19-Diterpenoid alkaloids displayed moderate to high antiviral activity against TMV and CMV at 500 μg/mL, dosage plays an important role in antiviral activities. This paper is the first report on the evolution of aconite diterpenoid alkaloids for antiviral activity against CMV.     

Preparation of New Sargassum fusiforme Polysaccharide Long-Chain Alkyl Group Nanomicelles and Their Antiviral Properties against ALV-J

Avian leukosis virus subgroup J (ALV-J) is an immunosuppressive virus which has caused heavy losses to the poultry breeding industry. Currently, there is no effective medicine to treat this virus. In our previous experiments, the low-molecular-weight Sargassum fusiforme polysaccharide (SFP) was proven to possess antiviral activity against ALV-J, but its function was limited to the virus adsorption stage. In order to improve the antiviral activity of the SFP, in this study, three new SFP long-chain alkyl group nanomicelles (SFP-C12M, SFP-C14M and SFP-C16M) were prepared. The nanomicelles were characterized according to their physical and chemical properties. The nanomicelles were characterized by particle size, zeta potential, polydispersity index, critical micelle concentration and morphology. The results showed the particle sizes of the three nanomicelles were all approximately 200 nm and SFP-C14M and SFP-C16M were more stable than SFP-C12M. The newly prepared nanomicelles exhibited a better anti-ALV-J activity than the SFP, with SFP-C16M exhibiting the best antiviral effects in both the virus adsorption stage and the replication stage. The results of the giant unilamellar vesicle exposure experiment demonstrated that the new virucidal effect of the nanomicelles might be caused by damage to the phospholipid membrane of ALV-J. This study provides a potential idea for ALV-J prevention and development of other antiviral drugs.     

Synthesis and Antiviral Activities of Chiral Thiourea Derivatives

An environmentally benign method has been developed for the synthesis of novel chiral thiourea derivatives in high yields in ionic liquid [Bmim]PF6. The ionic solvent can be recovered and reused without any loss of its activity. The target compounds were characterized by elemental analysis, IR, 1H NMR and 13C NMR spectral data. According to the preliminary bioassay, some of the chiral thiourea analogues exhibited moderate in vivo antiviral activities against TMV at a concentration of 500 mg/L. Title chiral compound 3i was found to possess good in vivo protection, inactivation and curative activities of 57.0%, 96.4% and 55.0%, respectively against TMV with an inhibitory concentration at 500 mg/L. The title chiral compound 3i revealed better inactivation effect on TMV (EC50＝50.8 µg/mL) than Ningnanmycin (EC50＝60.2 µg/mL).     

Therapeutic Potential of 2-Methylquinazolin-4(3H)-one as an Antiviral Agent against Influenza A Virus-Induced Acute Lung Injury in Mice

Qingdai-Mabo (QM), a traditional Chinese herbal formula composed of medicinal herb and fungus, has been used for treatment of cough and viral pneumonia. However, the underlying mechanism and bioactive components against anti-influenza A virus remain unclear. In the present study, ethyl acetate (EA) extract of QM decoctions was tested for its biological activity against acute lung injury (ALI) and its main components were identified using UPLC−MS/MS. In total, 18 bioactive components were identified, including 2-Methylquinaozlin-4(3H)-one (C1), which showed significant antiviral activity in vitro with an IC₅₀ of 23.8 μg/mL. Furthermore, we validated the efficacy of C1 in ameliorating ALI lesions and inflammation in influenza A virus-infected mice. The results showed that C1 significantly reduced the lung index, downregulated neuraminidase (NA) and nucleoprotein (NP), and decreased the expression of pro-inflammatory molecules IFN-α, TNF-α, MCP-1, IL-6, and IL-8; however, they enhanced levels of IL-10 and IFN-γ in lung homogenate from mice infected by influenza A virus. In addition, C1 inhibited the recruitment of macrophages. These in vitro and in vivo studies suggested that the significant anti-influenza A virus activity contributed to its curative effect on lesions and inflammation of viral pneumonia in mice. Given its potential antiviral activity against influenza A virus, C1 is determined to be a main active component in the EA extract of QM. Taken together, the antiviral activity of C1 suggests its potential as an effective treatment against viral pneumonia via the inhibition of virus replication, but the mechanism C1 on antiviral research needs to be explored further.     

Non-Covalent Reactions Supporting Antiviral Development

Viruses are the current big enemy of the world’s healthcare systems. As the small infector causes various deadly diseases, from influenza and HIV to COVID-19, the virus continues to evolve from one type to its mutants. Therefore, the development of antivirals demands tremendous attention and resources for drug researchers around the world. Active pharmaceutical ingredients (API) development includes discovering new drug compounds and developing existing ones. However, to innovate a new antiviral takes a very long time to test its safety and effectiveness, from structure modeling to synthesis, and then requires various stages of clinical trials. Meanwhile, developing the existing API can be more efficient because it reduces many development stages. One approach in this effort is to modify the solid structures to improve their physicochemical properties and enhance their activity. This review discusses antiviral multicomponent systems under the research phase and has been marketed. The discussion includes the types of antivirals, their counterpart compound, screening, manufacturing methods, multicomponent systems yielded, characterization methods, physicochemical properties, and their effects on their pharmacological activities. It is hoped that the opportunities and challenges of solid antiviral drug modifications can be drawn in this review as important information for further antiviral development.     

Secondary Metabolites from Marine Sources with Potential Use as Leads for Anticancer Applications

The development of novel anticancer agents is essential to finding new ways to treat this disease, one of the deadliest diseases. Some marine organisms have proved to be important producers of chemically active compounds with valuable bioactive properties, including anticancer. Thus, the ocean has proved to be a huge source of bioactive compounds, making the discovery and study of these compounds a growing area. In the last few years, several compounds of marine origin, which include algae, corals, and sea urchins, have been isolated, studied, and demonstrated to possess anticancer properties. These compounds, mainly from securamines and sterols families, have been tested for cytotoxic/antiproliferative activity in different cell lines. Bioactive compounds isolated from marine organisms in the past 5 years that have shown anticancer activity, emphasizing the ones that showed the highest cytotoxic activity, such as securamines H and I, cholest-3β,5α,6β-triol, (E)-24-methylcholest-22-ene-3β,5α,6β-triol, 24-methylenecholesta-3β,5α,6β-triol, and 24-methylcholesta-3β,5α,6β-triol, will be discussed in this review. These studies reveal the possibility of new compounds of marine origin being used as new therapeutic agents or as a source of inspiration to develop new therapeutic agents.     

Development and Effects of Influenza Antiviral Drugs

Influenza virus is a highly contagious zoonotic respiratory disease that causes seasonal outbreaks each year and unpredictable pandemics occasionally with high morbidity and mortality rates, posing a great threat to public health worldwide. Besides the limited effect of vaccines, the problem is exacerbated by the lack of drugs with strong antiviral activity against all flu strains. Currently, there are two classes of antiviral drugs available that are chemosynthetic and approved against influenza A virus for prophylactic and therapeutic treatment, but the appearance of drug-resistant virus strains is a serious issue that strikes at the core of influenza control. There is therefore an urgent need to develop new antiviral drugs. Many reports have shown that the development of novel bioactive plant extracts and microbial extracts has significant advantages in influenza treatment. This paper comprehensively reviews the development and effects of chemosynthetic drugs, plant extracts, and microbial extracts with influenza antiviral activity, hoping to provide some references for novel antiviral drug design and promising alternative candidates for further anti-influenza drug development.     

Antiviral Activities of Halogenated Emodin Derivatives against Human Coronavirus NL63

The current COVID-19 outbreak has highlighted the need for the development of new vaccines and drugs to combat Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Recently, various drugs have been proposed as potentially effective against COVID-19, such as remdesivir, infliximab and imatinib. Natural plants have been used as an alternative source of drugs for thousands of years, and some of them are effective for the treatment of various viral diseases. Emodin (1,3,8-trihydroxy-6-methylanthracene-9,10-dione) is a biologically active anthraquinone with antiviral activity that is found in various plants. We studied the selectivity of electrophilic aromatic substitution reactions on an emodin core (halogenation, nitration and sulfonation), which resulted in a library of emodin derivatives. The main aim of this work was to carry out an initial evaluation of the potential to improve the activity of emodin against human coronavirus NL63 (HCoV-NL63) and also to generate a set of initial SAR guidelines. We have prepared emodin derivatives which displayed significant anti-HCoV-NL63 activity. We observed that halogenation of emodin can improve its antiviral activity. The most active compound in this study was the iodinated emodin analogue E_3I, whose anti-HCoV-NL63 activity was comparable to that of remdesivir. Evaluation of the emodin analogues also revealed some unwanted toxicity to Vero cells. Since new synthetic routes are now available that allow modification of the emodin structure, it is reasonable to expect that analogues with significantly improved anti-HCoV-NL63 activity and lowered toxicity may thus be generated.     

The Biosynthesized Zinc Oxide Nanoparticles’ Antiviral Activity in Combination with Pelargonium zonale Extract against the Human Corona 229E Virus

Almost one-third of all infectious diseases are caused by viruses, and these diseases account for nearly 20% of all deaths globally. It is becoming increasingly clear that highly contagious viral infections pose a significant threat to global health and economy around the world. The need for innovative, affordable, and safe antiviral therapies is a must. Zinc oxide nanoparticles are novel materials of low toxicity and low cost and are known for their antiviral activity. The genus Pelargonium was previously reported for its antiviral and antimicrobial activity. In this work, Pelargonium zonale leaf extract chemical profile was studied via high-performance liquid chromatography (HPLC) and was used for the biosynthesis of zinc oxide nanoparticles. Furthermore, the antiviral activity of the combination of P. zonale extract and the biosynthesized nanoparticles of ZnO against the human corona 229E virus was investigated. Results revealed that ZnONPs had been biosynthesized with an average particle size of about 5.5 nm and characterized with UV, FTIR, TEM, XRD, and SEM. The antiviral activity showed significant activity and differences among the tested samples in favor of the combination of P. zonale extract and ZnONPs (ZnONPs/Ex). The lowest IC_50, 2.028 µg/mL, and the highest SI, 68.4 of ZnONPs/Ex, assert the highest antiviral activity of the combination against human coronavirus (229E).     

Antiviral properties from plants of the Mediterranean flora

Natural products are a successful source in drug discovery, playing a significant role in maintaining human health. We investigated the in vitro cytotoxicity and antiviral activity of extracts from 18 traditionally used Mediterranean plants. Noteworthy antiviral activity was found in the extract obtained from the branches of Daphne gnidium L. against human immunodeficiency virus type-1 (EC₅₀ = 0.08 μg/mL) and coxsackievirus B5 (EC₅₀ = 0.10 μg/mL). Other relevant activities were found against BVDV, YFV, Sb-1, RSV and HSV-1. Interestingly, extracts from Artemisia arborescens L. and Rubus ulmifolius Schott, as well as those from D. gnidium L., showed activities against two different viruses. This extensive antiviral screening allowed us to identify attractive activities, offering opportunities to develop lead compounds with a great pharmaceutical potential.