Respiratory viral infections present significant global health challenges, causing substantial morbidity and mortality, particularly among highly susceptible components of the population. The emergence of pandemics and epidemics, such as those caused by influenza viruses and coronaviruses, emphasizes the urgent need for effective antiviral therapeutics. In this review, we explore the potential of broad-spectrum antiviral agents targeting respiratory RNA viruses, including influenza viruses, coronaviruses, respiratory syncytial virus, human metapneumovirus, human parainfluenza viruses, and rhinoviruses. Various broad-spectrum direct-acting and host-targeting antivirals are discussed, including monoclonal antibodies targeting conserved regions of viral surface proteins, molecules interfering with host cell receptors or viral replication machinery, viral protease inhibitors, siRNA therapies, ribonuclease, and 3D8 scFv. Advancements in host-targeting approaches to reduce resistance and RNA-based therapeutics offer significant potential for combating respiratory viral threats. Despite challenges, broad-spectrum antiviral agents represent a crucial strategy, particularly when specific viral pathogens are unidentified or rapid intervention is essential, such as during pandemics or outbreaks.

The virus behind the current pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the etiology of novel coronavirus disease (COVID-19) and poses a critical public health threat worldwide. Effective therapeutics and vaccines against multiple coronaviruses remain unavailable. Single-chain variable fragment (scFv), a recombinant antibody, exhibits broad-spectrum antiviral activity against DNA and RNA viruses owing to its nucleic acid-hydrolyzing property. The antiviral activity of 3D8 scFv against SARS-CoV-2 and other coronaviruses was evaluated in Vero E6 cell cultures. Viral growth was quantified with quantitative RT-qPCR and plaque assay. The nucleic acid-hydrolyzing activity of 3D8 was assessed through abzyme assays of in vitro viral transcripts and cell viability was determined by MTT assay. We found that 3D8 inhibited the replication of SARS-CoV-2, human coronavirus OC43 (HCoV-OC43), and porcine epidemic diarrhea virus (PEDV). Our results revealed the prophylactic and therapeutic effects of 3D8 scFv against SARS-CoV-2 in Vero E6 cells. Immunoblot and plaque assays showed the reduction of coronavirus nucleoproteins and infectious particles, respectively, in 3D8 scFv-treated cells. These data demonstrate the broad-spectrum antiviral activity of 3D8 against SARS-CoV-2 and other coronaviruses. Thus, it could be considered a potential antiviral countermeasure against SARS-CoV-2 and zoonotic coronaviruses.

Outbreaks of viral diseases, which cause morbidity and mortality in animals and humans, are increasing annually worldwide. Vaccines, antiviral drugs, and antibody therapeutics are the most effective tools for combating viral infection. The ongoing coronavirus disease 2019 pandemic, in particular, raises an urgent need for the development of rapid and broad-spectrum therapeutics. Current antiviral drugs and antiviral antibodies, which are mostly specific at protein levels, have encountered difficulties because the rapid evolution of mutant viral strains resulted in drug resistance. Therefore, degrading viral genomes is considered a novel approach for developing antiviral drugs. The current article highlights all potent candidates that exhibit antiviral activity by digesting viral genomes such as RNases, RNA interference, interferon-stimulated genes 20, and CRISPR/Cas systems. Besides that, we introduce a potential single-chain variable fragment (scFv) that presents antiviral activity against various DNA and RNA viruses due to its unique nucleic acid hydrolyzing characteristic, promoting it as a promising candidate for broad-spectrum antiviral therapeutics.

Emerging Oseltamivir-resistant influenza strains pose a critical public health threat due to antigenic shifts and drifts. We report an innovative strategy for controlling influenza A infections by use of a novel minibody of the 3D8 single chain variable fragment (scFv) showing intrinsic viral RNA hydrolyzing activity, cell penetration activity, and epidermal cell penetration ability. In this study, we examined 3D8 scFv’s antiviral activity in vitro on three different H1N1 influenza strains, one Oseltamivir-resistant (A/Korea/2785/2009pdm) strain, and two Oseltamivir-sensitive (A/PuertoRico/8/1934 and A/X-31) strains. Interestingly, the 3D8 scFv directly digested viral RNAs in the ribonucleoprotein complex. scFv’s reduction of influenza viral RNA including viral genomic RNA, complementary RNA, and messenger RNA during influenza A infection cycles indicated that this minibody targets all types of viral RNAs during the early, intermediate, and late stages of the virus’s life cycle. Moreover, we further addressed the antiviral effects of 3D8 scFv to investigate in vivo clinical outcomes of influenza-infected mice. Using both prophylactic and therapeutic treatments of intranasal administered 3D8 scFv, we found that Oseltamivir-resistant H1N1-infected mice showed 90% (prophylactic effects) and 40% (therapeutic effects) increased survival rates, respectively, compared to the control group. The pathological signs of influenza A in the lung tissues, and quantitative analyses of the virus proliferations supported the antiviral activity of the 3D8 single chain variable fragment. Taken together, these results demonstrate that 3D8 scFv has antiviral therapeutic potentials against a wide range of influenza A viruses via the direct viral RNA hydrolyzing activity.

Background/Objectives: Cancer cachexia is a multifactorial syndrome characterized by the progressive loss of skeletal muscle mass and adipose tissue. Dalbergia odorifer is widely used in traditional medicine in Korea and China to treat various diseases. However, its exact role and underlying mechanism in regulating cancer cachexia have not been elucidated yet. This research was conducted to investigate the effect of D. odorifer extract (DOE) in preventing the development of cancer-induced cachexia symptoms and figure out the relevant mechanisms. Methods: A cancer cachexia model was established in Balb/c mice using the CT26 colon carcinoma cell line. To evaluate the anti-cachexia effect of Dalbergia odorifer extract (DOE), CT26-bearing mice were orally administered with DOE at concentrations of 50 and 100 mg/kg BW for 14 days. C2C12 myotubes and 3T3L1 adipocytes were treated with 80% CT26 conditioned medium, DOE, and wortmannin, a particular AKT inhibitor to determine the influence of DOE in the AKT signaling pathway. Mice body weight, food intake, myofiber cross-sectional area, adipocyte size, myotube diameter, lipid accumulation, and relevant gene expression were analyzed. Results: The oral administration of DOE at doses of 50 and 100 mg/kg body weight to CT26 tumor-bearing mice resulted in a significant reduction in body weight loss, an increase in food intake, and a decrease in serum glycerol levels. Furthermore, DOE treatment led to an increase in muscle mass, larger muscle fiber diameter, and elevated expression levels of MyH2 and Igf1, while simultaneously reducing the expression of Atrogin1 and MuRF1. DOE also attenuated adipose tissue wasting, as evidenced by increased epididymal fat mass, enlarged adipocyte size, and upregulated Pparγ expression, alongside a reduction in Ucp1 and IL6 levels. In cachectic C2C12 myotubes and 3T3-L1 adipocytes induced by the CT26 conditioned medium, DOE significantly inhibited muscle wasting and lipolysis by activating the AKT signaling pathway. The treatment of wortmannin, a specific AKT inhibitor, effectively neutralized DOE’s impact on the AKT pathway, myotube diameter, and lipid accumulation. Conclusions: DOE ameliorates cancer cachexia through the expression of genes involved in protein synthesis and lipogenesis, while suppressing those related to protein degradation, suggesting its potential as a plant-derived therapeutic agent in combating cancer cachexia.

Influenza pandemics have had devastating impacts in the 20th and 21st centuries, resulting in millions of deaths. It is challenging to control the influenza virus through antiviral drugs due to its rapid evolution to evade the host immune system. The 3D8 single chain variable fragment (scFv) protein, known for its nuclease activity against DNA and RNA viruses, has demonstrated broad antiviral properties in various models. In this study, we investigated the impact of administration routes and dosages on the distribution of exogenously administered 3D8 scFv. Our results suggested that repeated intranasal (IN) injection primarily targets lung tissue, while intravenous (IV) administration ensures systemic distribution, including lung tissues via the bloodstream. Furthermore, we explored the efficacy of exogenous and endogenous 3D8 scFv in inhibiting influenza A virus (H1N1/PR8) replication in mouse models. Our findings revealed that while both approaches exhibited antiviral activity, with constitutive pre-infection expression of 3D8 scFv showed 100% survival, whereas mice receiving exogenous 3D8 scFv post-infection exhibited 33.3% survival. These findings highlight the potential of 3D8 scFv as a promising antiviral strategy against influenza and suggest its possible applications in transgenic livestock for future disease control.