Potential of antiviral therapy and prophylaxis for controlling RNA viral infections of livestock

2008 ◽  
Vol 78 (1) ◽  
pp. 170-178 ◽  
Author(s):  
Nesya Goris ◽  
Frank Vandenbussche ◽  
Kris De Clercq
2021 ◽  
Vol 118 (39) ◽  
pp. e2104759118
Author(s):  
Danielle E. Anderson ◽  
Jin Cui ◽  
Qian Ye ◽  
Baoying Huang ◽  
Ya Tan ◽  
...  

Bats are responsible for the zoonotic transmission of several major viral diseases, including those leading to the 2003 SARS outbreak and likely the ongoing COVID-19 pandemic. While comparative genomics studies have revealed characteristic adaptations of the bat innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the viral tolerance in bats. Here we report the establishment of genome-wide RNA interference (RNAi) and CRISPR libraries for the screening of the model megabat, Pteropus alecto. We used the complementary RNAi and CRISPR libraries to interrogate P. alecto cells for infection with two different viruses: mumps virus and influenza A virus, respectively. Independent screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells and human cells. The MTHFD1 inhibitor, carolacton, potently blocked replication of several RNA viruses, including SARS-CoV-2. We also discovered that bats have lower expression levels of MTHFD1 than humans. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad-spectrum antiviral therapy.


2020 ◽  
Vol 7 ◽  
Author(s):  
Angela Holly Villamagna ◽  
Sara J. Gore ◽  
James S. Lewis ◽  
J. Stone Doggett

Respiratory failure due to SARS-CoV-2 has caused widespread mortality, creating an urgent need for effective treatments and a long-term need for antivirals for future emergent coronaviruses. Pharmacotherapy for respiratory viruses has largely been unsuccessful with the exception of early treatment of influenza viruses, which shortens symptom duration and prevents infection in close contacts. Under the rapidly evolving circumstances of the COVID-19 pandemic, most clinical trials of experimental treatments in the United States have focused on later stages of the disease process. Worldwide, the clinical studies of the most impactful drugs, remdesivir and dexamethasone in ACTT-1, RECOVERY, and Solidarity, have studied hospitalized patients. Less than half of clinical trials in the U.S. have investigated oral agents, and the majority have taken place in hospitals at a disease stage where the viral load is already decreasing. The limited success of treatments for respiratory viruses and the viral dynamics of COVID-19 suggest that an antiviral therapy with the greatest impact against pandemic coronaviruses would be orally administered, well-tolerated, target a highly conserved viral protein or host-coronavirus interaction and could be used effectively throughout the world, including resource-poor settings. We examine the treatment of respiratory viral infections and current clinical trials for COVID-19 to provide a framework for effective antiviral therapy and prevention of future emergent coronaviruses and call attention to the need for continued preclinical drug discovery.


2018 ◽  
Vol 99 (2) ◽  
pp. 215-223 ◽  
Author(s):  
E P Tikhonova ◽  
T Yu Kuz'mina ◽  
N V Andronova ◽  
O A Tyushevskaya ◽  
T A Elistratova ◽  
...  

Aim. Comparative study of clinical efficacy and safety of antiviral drug triazavirin and umifenovir in the treatment of patients with acute respiratory viral infections and influenza. Methods. The study included 100 patients aged 18 to 65 years diagnosed with moderate acute respiratory viral infection. Group 1 included 34 patients receiving umifenovir 200 mg 4 times a day for 5 days, and comparison group included 32 patients who received triazavirin 1 capsule (250 mg) 3 times a day for 5 days. Group 3 (control group) included 34 patients not treated with antiviral therapy. Efficacy and safety of the studied antiviral drugs were evaluated based on clinical symptoms in the disease course and were confirmed by adaptive reactions of the organism. Results. Among patients receiving triazavirin, recovery time and fever, headache and catarrhal syndrome resolution time were less than among patients who received umifenovir. On triazavirin treatment with favorable tolerability, symptomatic medications (antipyretics) were discontinued, and the duration of their use was less, than in patients receiving umifenovir. Evaluation of clinical efficacy of umifenovir and triazavirin for the treatment of acute respiratory viral infections and influenza demonstrated that the drugs effectively reverse the main symptoms of the disease (p <0.05), reduce complications incidence (18.1±2.1% vs. 55.9±3.2%, p <0.05) and contribute to the stabilization of adaptive reactions of the organism in contrast to the results of patients not receiving etiotropic therapy (6.9±2.9% vs. 12.8±2.7, p <0.05). During the use of umifenovir by day 4 and during the use of triazavirin by day 3 intoxication and catarrhal syndromes had been reversed, while in case of the absence of antiviral therapy, 55.8% of patients had continuing intoxication and catarrhal symptoms. Conclusion. The results of the study allow defining umifenovir and triazavirin as the first line of defense against acute respiratory viral infections with good efficacy and tolerability of the drugs.


2019 ◽  
pp. 183-187 ◽  
Author(s):  
E. A. Dondurey ◽  
E. V. Obraztsova ◽  
Yu. S. Semiletko ◽  
N. V. Ovchinnikova ◽  
E. G. Golovacheva ◽  
...  

In the context of the wide range of products recommended for antiviral therapy, there is still a need for continuous evaluation of their effectiveness and safety in pediatrics. The work describes the experience of non-interventional study of the domestic drug umifenovir in the modern clinical practice. The authors studied 216 case histories of children hospitalized with acute respiratory viral infections at early stages of the disease. Against the background of the drug administration a significant reduction in the duration of all symptoms of the infectious process and the need to prescribe antibiotic therapy to patients, a reduction in the chances of complicated flu and acute respiratory viral infections, as well as a favorable safety spectrum and a high level of compliance during treatment.


2016 ◽  
Vol I (I) ◽  
pp. 12-20
Author(s):  
Mubashar Rehman

With time viral infections are increasing day by day due to various reasons like new viruses, the resistance of viruses to antiviral therapy, and mutation of one form of the virus to another form; these types of problems create many challenges in the field of research. Furthermore, a lot of challenges are encountered in the treatment of antiviral therapy, like interaction with other medication and use of increased frequency and a high dose of antiviral due to infection in CNS or synovial fluid where drug permeation is less. Consequently, toxicity and other side effect chances will be more. Nano-technological approaches are used to overcome these challenges. The beneficial properties come from such engineering, including stimuli sensitivity, targetability, and longevity; these are all combined to give multifunctional nano-carriers that concurrently execute different beneficial tasks


2020 ◽  
Vol 4 (1) ◽  
pp. 020-027
Author(s):  
Nikhra Vinod

The global virome: The viruses have a global distribution, phylogenetic diversity and host specificity. They are obligate intracellular parasites with single- or double-stranded DNA or RNA genomes, and afflict bacteria, plants, animals and human population. The viral infection begins when surface proteins bind to receptor proteins on the host cell surface, followed by internalisation, replication and lysis. Further, trans-species interactions of viruses with bacteria, small eukaryotes and host are associated with various zoonotic viral diseases and disease progression. Virome interface and transmission: The cross-species transmission from their natural reservoir, usually mammalian or avian, hosts to infect human-being is a rare probability, but occurs leading to the zoonotic human viral infection. The factors like increased human settlements and encroachments, expanded travel and trade networks, altered wildlife and livestock practices, modernised and mass-farming practices, compromised ecosystems and habitat destruction, and global climate change have impact on the interactions between virome and its hosts and other species and act as drivers of trans-species viral spill-over and human transmission. Zoonotic viral diseases and epidemics: The zoonotic viruses have caused various deadly pandemics in human history. They can be further characterized as either newly emerging or re-emerging infectious diseases, caused by pathogens that historically have infected the same host species, but continue to appear in new locations or in drug-resistant forms, or reappear after apparent control or elimination. The prevalence of zoonoses underlines importance of the animal–human–ecosystem interface in disease transmission. The present COVID-19 infection has certain distinct features which suppress the host immune response and promote the disease potential. Treatment for epidemics like covid-19: It appears that certain nutraceuticals may provide relief in clinical symptoms to patients infected with encapsulated RNA viruses such as influenza and coronavirus. These nutraceuticals appear to reduce the inflammation in the lungs and help to boost type 1 interferon response to these viral infections. The human intestinal microbiota acting in tandem with the host’s defence and immune system, is vital for homeostasis and preservation of health. The integrity and balanced activity of the gut microbes is responsible for the protection from disease states including viral infections. Certain probiotics may help in improving the sensitivity and effectivity of immune system against viral infections. Currently, antiviral therapy is available only for a limited number of zoonotic viral infections. Because viruses are intracellular parasites, antiviral drugs are not able to deactivate or destroy the virus but can reduce the viral load by inhibiting replication and facilitating the host’s innate immune mechanisms to neutralize the virus. Conclusion: Lessons from recent viral epidemics - Considering that certain nutraceuticals have demonstrated antiviral effects in both clinical and animal studies, further studies are required to establish their therapeutic efficacy. The components of nutraceuticals such as luteolin, apigenin, quercetin and chlorogenic acid may be useful for developing a combo-therapy. The use of probiotics to enhance immunity and immune response against viral infections is a novel possibility. The available antiviral therapy is inefficient in deactivating or destroying the infecting viruses, may help in reducing the viral load by inhibiting replication. The novel efficient antiviral agents are being explored.


2017 ◽  
Vol 89 (1) ◽  
pp. 62-71 ◽  
Author(s):  
V A Bulgakova ◽  
A A Poromov ◽  
A I Grekova ◽  
N Yu Pshenichnaya ◽  
E P Selkova ◽  
...  

Aim. To identify risk factors (RFs) for the development of bacterial complications and the prolonged course of influenza and other acute respiratory viral infections (ARVIs) among inpatients treated in Russian healthcare facilities in the post-pandemic period; to determine the clinical presentation of the disease (flu-like syndrome) in risk-group people and to evaluate the efficacy of antiviral therapy with arbidol (umifenovir). Materials and methods. The investigators retrospectively analyzed randomly selected medical records of inpatients with influenza and other ARVI in 88 hospitals from 50 regions of the Russian Federation: those of 3532 and 1755 patients in the 2010-2011 and 2014-2015 seasons, respectively, by applying parametric and nonparametric statistical methods. Results. The built database of patients with influenza-like syndrome contained data from the histories of 2072 men and 2537 women, of whom there were 317 (12.49%) pregnant women; gender evidence was not given in the medical records for 678 patients. 382 (7.2%) were vaccinated against influenza. 1528 (28.9%) people were admitted to hospital with various complications. Information on laboratory tests was available in 1691 (31.98%) patients; of these, 1291 (76.4%) were detected to have influenza and other respiratory viruses. Influenza viruses were found in 1026 (60.7%) examinees; influenza A viruses in 712 (42.1%) people while pandemic strain of swine influenza A/H1N1 and A/H3N2 viruses was detected in 487 (28.8%) and 107 (6.3%) patients, respectively; influenza A subtype was indicated in 118 (7%) persons with laboratory-confirmed influenza virus. Influenza B viruses were found in 314 (18.6%) examinees. Other types of respiratory viruses were detected in 265 (15.7%) patients. The body mass index exceeded 30 kg/m2 in 227 (4.3%) patients. Single-factor analysis of variance revealed factors influencing the course of flu-like syndrome and identified risk groups: children younger than 2 years old and adults over 65, pregnant women, and people with chronic somatic diseases and obesity. The high-risk groups exhibited a more severe course of flu-like syndrome than did the patients outside the risk groups. The incidence of complications was higher, especially in the under 2-year-year-old children and in patients with endocrine, metabolic, or respiratory diseases, with a large proportion of complications being pneumonia. The efficacy of antiviral therapy was higher in the elderly, patients with chronic diseases, and pregnant women than in patients not at risk. In patients treated with umifenovir (provided that it was administered in the first 48 hours after disease onset), the duration of fever and frequency of complications proved to be lower than those in patients who did not receive antiviral therapy. Conclusion. The FRs for influenza and ARVI complications are patient’s age (children under 3 years of age and adults older than 65 years), the presence of chronic somatic diseases, and pregnancy. Patients with endocrine, eating, metabolic (including obesity), circulatory, and respiratory disorders are at high risk for influenza and ARVI complications. Umifenovir therapy substantially reduces the duration of fever and risk of complications, especially in patients with laboratory-confirmed influenza infection


Author(s):  
Danielle E Anderson ◽  
Jin Cui ◽  
Qian Ye ◽  
Baoying Huang ◽  
Wenhong Zu ◽  
...  

SUMMARYBats are responsible for the zoonotic transmission of several major viral diseases including the 2003 SARS outbreak and the ongoing COVID-19 pandemic. While bat genomic sequencing studies have revealed characteristic adaptations of the innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the tolerance of viral infections in bats. Here we report the establishment and screening of genome-wide RNAi library and CRISPR library for the model megabat, Pteropus Alecto. We used the complementary RNAi and CRISPR libraries to interrogate Pteropus Alecto cells for infection with two different viruses, mumps virus and Influenza A virus, respectively. Screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C-1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells as well as in human cells. MTHFD1 inhibitor carolacton potently blocked replication of several RNA viruses including SARS-CoV-2. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad spectrum antiviral therapy.


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