The current COVID-19 pandemic contributed by the SARS-CoV-2 has put in place an urgent need for new and promising antiviral therapeutics. The viral RNA-dependent RNA polymerase (RdRp) enzyme plays a vital role in viral replication for all RNA viruses, including SARS-CoV-2, thereby making it a prime and promising candidate for novel antiviral targeting. Interestingly, the human telomerase reverse transcriptase (hTERT), a common catalytic subunit of the telomerase enzyme in many cancers, has also been identified with structural and functional similarities to the viral RdRp. Therefore, it becomes essential to evaluate and consider anticancer drugs that target hTERT towards antiviral RdRp activity, and vice versa. For instance, Floxuridine, an hTERT inhibitor, and VX-222, a hepatitis C virus RdRp inhibitor, are now gaining recognition as a potential antiviral against SARS-CoV-2 and anti-hTERT for cancer, simultaneously. While limited studies on hTERT inhibitors for use as viral RdRp, and anti-RdRp inhibitors as hTERT inhibitors are available, in this review, we aim at bringing to light this close structural and functional relationship between both these enzymes. We punctuate this idea with specific examples on how potential anticancer inhibitors can effectively be brought to use as inhibitors against the SARS-CoV-2 virus, a relatively new pathogen, compared to the very well-studied field of cancer research.

Zn deficiency compromises its biological functions, its effect on the immune system and its antiviral activity, increasing vulnerability to infectious diseases. This narrative review aims at presenting and discussing functional aspects and possible mechanisms involved in the potential role of Zn in the immune response and antiviral activity for coronavirus infectious disease-19 (COVID-19) prevention and control. The searches were conducted in PubMed and Science Direct databases, using clinical trials, experimental studies in animals and humans, case–control studies, case series, letters to the editor, and review articles published in English, without restrictions on year of publication. Search approach was based on using the terms: ‘zinc’, ‘COVID-19’, ‘antiviral agents’, ‘immunologic factors’ and ‘respiratory tract infections’. Literature shows the importance of Zn as an essential mineral immunomodulator with relevant antiviral activity in the body. Thus, although there is still a scarcity of studies evaluating Zn supplementation in patients with COVID-19, the results on the topic show the necessity of controlling Zn mineral deficiency, as well as maintaining its homoeostasis in the body in order to strengthen the immune system and improve the prevention of highly complex viral infections, such as that of the COVID-19.

Many psychiatric patients have been infected with COVID-19, and patients with COVID-19 may develop psychiatric symptoms after treatment with antiviral drugs. Given the tolerability and minimal P450 interactions, antidepressants (i.e., citalopram, escitalopram etc.), antipsychotics (i.e., olanzapine) and valproate can be considered to be safe in combination with antiviral drugs.

The poultry industry is affected by economically important problems such as Newcastle disease (ND). Newcastle disease virus (NDV) belongs to the Paramyxoviridae family and manifests as different strains; lentogenic, mesogenic and velogenic. ND affects the quality of eggs and impairs growth performance of birds. Various efforts have been made to control economic losses due to this disease, including using live and killed vaccines, which do not confer 100% immunity in all cases. Due to mutations within viral strains, NDV can become resistant and difficult to control, and there is a need to search for alternative measures. Medicinal plants are considered as a complementary means to control this virus, especially in developing countries, because they have been implicated in treatments for a variety of infectious and non-infectious diseases. Alkaloids, flavonoids, saponins and tannins found in plants have been regarded as novel antiviral agents. The following paper encompasses the studies related to plants having in vitro antiviral activity against ND such as Momordica balamina, Adansonia digitata, Artemisia annua, Azadirachta indica, Psidium guajava, Moringa oleifera and plants having good in vivo antiviral activity such as Aloe secundiflora, Cucumis metuliferus and Anthocleista nobilis as well. It discusses plants with the potential to improve the immunity of infected birds, such as Mangrove halophytes, Nigella sativa, Polysavone, Melissa officinalis, Momordica cochinchinensis, Echinacea purpurea, Withania somnifera and Aspargus Racemosus.

Viral disease is one of the major causes of financial loss and animal suffering in today's cattle industry. Increases in global commerce and average herd size, urbanization, vertical integration within the industry and alterations in global climate patterns have allowed the spread of pathogenic viruses, or the introduction of new viral species, into regions previously free of such pathogens, creating the potential for widespread morbidity and mortality in naïve cattle populations. Despite this, no antiviral products are currently commercially licensed for use in bovine medicine, although significant progress has been made in the development of antivirals for use against bovine viral diarrhea virus (BVDV), foot and mouth disease virus (FMDV) and bovine herpesvirus (BHV). BVDV is extensively studied as a model virus for human antiviral studies. Consequently, many compounds with efficacy have been identified and a few have been successfully used to prevent infection in vivo although commercial development is still lacking. FMDV is also the subject of extensive antiviral testing due to the importance of outbreak containment for maintenance of export markets. Thirdly, BHV presents an attractive target for antiviral development due to its worldwide presence. Antiviral studies for other bovine viral pathogens are largely limited to preliminary studies. This review summarizes the current state of knowledge of antiviral compounds against several key bovine pathogens and the potential for commercial antiviral applications in the prevention and control of several selected bovine diseases.

Many animal and human viruses are disseminated via semen, but there is little information on how to measure and stimulate protective antiviral immunity in the male reproductive tract and semen. This information is important since successful vaccination through the stimulation of protective immune responses could be a mechanism to prevent viral contamination of semen and subsequent wide spread viral dissemination. Even control of the infection by shortening the duration of viral shedding and lowering the viral load in semen would lessen the chances of viral dissemination through this route. This review will highlight the current knowledge of immunity in the male reproductive tract and summarize ‘antiviral’ as well as ‘proviral’ factors in semen such as cytokines, cells, antibodies, antimicrobial peptides, enzymes, hormones and growth factors. These factors must provide a fine balance between ‘immunosuppression’ in semen needed to protect sperm viability and ‘immunocompetency’ to prevent pathogen contamination. The review will also suggest continuing challenges to researchers for preventing viral dissemination via semen and propose a large animal model for continued research in this important area.

This study describes the in vitro antiviral activity of two species of oyster hemolymph (Crassostrea rhizophorae and C. gigas) collected on Southern Brazilian coastline. Either the acellular and cellular fractions were tested against herpes simplex type-1 (HSV-1), human adenovirus respiratory strain (AdV-5) and simian rotavirus (RV-SA11) by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The evaluation of viral inhibition was performed using four different strategies: simultaneous, pre-infection and post-infection treatments and virucidal assays. The cellular fraction from Crassostrea rhizophorae showed the most prominent inhibition of HSV-1 and AdV-5 replication, particularly in post-infection treatment assay. No inhibition of rotavirus replication was observed. Both oyster hemolymph fractions showed virucidal activity against all tested virus in non-cytotoxic concentrations.

The in vivo evidence of the antimicrobial and antiviral activity of bovine milk and colostrum derived components are reviewed with special emphasis on lactoferrin and lactoperoxidase. Their mode of action and the rationale for their application in efficacy trials with rodents, farm animals, fish and humans, to give protection against infectious agents, are described. A distinction is made between efficacy obtained by oral and non-oral administration of these non-specific defence factors which can be commercially applied in large quantities due to major achievements in dairy technology. From the in vivo studies one can infer that lactoferrin and lactoperoxidase are very promising, naturally occurring antimicrobials for use in fish farming, husbandry, oral hygiene and functional foods. Other promising milk-derived compounds include lipids, from which anti-infective degradation products are generated during digestion, and antimicrobial peptides hidden in the casein molecules.

Ribonuclease-resistant RNA molecules that bind to infectious human cytomegalovirus (HCMV) were isolated in vitro from a pool of randomized sequences after 16 cycles of selection and amplification. The two ligands (L13 and L19) characterized exhibited high HCMV-binding affinity in vitro and effectively inhibited viral infection in tissue culture. Their antiviral activity was also specific as they only reacted with two different strains of HCMV but not with the related herpes simplex virus 1 and human cells. These two ligands appeared to function as antivirals by blocking viral entry. Ultraviolet (UV) crosslinking studies suggested that L13 and L19 bind to HCMV essential glycoproteins B and H, respectively. Thus, RNA ligands that bind to different surface antigens of HCMV can be simultaneously isolated by the selection procedure. Our study demonstrates the feasibility of using these RNA ligands as a research tool to identify viral proteins required for infectivity and as an antiviral agent to block viral infection.

The factors that influence the enhanced stability observed experimentally of human rhinovirus 14 (HRV14) upon binding a hydrophobic antiviral drug have been investigated by molecular dynamics. Simulations centered about the HRV14 drug-binding pocket allow the reliable assessment of differences in capsid protein motions of HRV14 and drug-bound HRV14. We propose that the experimentally observed stabilization of the ligated virus arises from higher entropy, rather than enthalpy. Time-averaged interaction energies between the viral protein and molecules occupying the pocket are less favorable in the presence of the drug, consistent with the proposal that the observed stability arises from entropic effects. Interaction energies characterizing subunit–subunit contacts within one viral protomer are found to be substantially stronger than those between two protomers. Such distinction in subunit interaction would have clear implications on assembly and disassembly. Drug binding is found to affect large-scale, collective properties, while leaving local atomic properties unperturbed. Specifically, the simulations reveal a weakening of long-range correlations in atomic motions upon drug binding. On the other hand, neither the fast time scale RMS fluctuations of individual atomic positions nor the fluctuation build-up curves from the capsid β-sandwich forming the drug-binding pocket show a consistent distinction between the drug-bound and drug-free viral simulations. Collectively, the detailed description available from the simulations provides an understanding of the experimental observations on the drug-induced changes in thermal stability and protease sensitivity reported for picornaviruses. The predicted significance of binding entropy can be explored experimentally and should be considered in the design of new antiviral compounds.