scholarly journals Screening for Anti-Influenza Actives of Prefractionated Traditional Chinese Medicines

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Qianli Kang ◽  
Yanyan Wang ◽  
Qinghua Cui ◽  
Lili Gong ◽  
Yong Yang ◽  
...  

Traditional Chinese medicines (TCMs) have proven to possess advantages in counteracting virus infections according to clinical practices. It’s therefore of great value to discover novel antivirals from TCMs. In this paper, One hundred medicinal plants which have been included in TCM prescriptions for antiviral treatment were selected and prefractionated into 5 fractions each by sequentially using cyclohexane, dichloromethane, ethyl acetate, n-butanol, and water. 500 TCM-simplified extracts were then subjected to a phenotypic screening using a recombinant IAV expressing Gaussia luciferase. Ten TCM fractions were identified to possess antiviral activities against influenza virus. The IC50’s of the hit fractions range from 1.08 to 6.45 μg/mL, while the SIs, from 7.52 to 98.40. Furthermore, all the ten hit fractions inhibited the propagation of progeny influenza virus significantly at 20 μg/mL. The hit TCM fractions deserve further isolation for responsible constituents leading towards anti-influenza drugs. Moreover, a library consisting of 500 simplified TCM extracts was established, facilitating antiviral screening in quick response to emerging and re-emerging viruses such as Ebola virus and current SARS-CoV-2 pandemic.

2020 ◽  
Vol 20 (4) ◽  
pp. 423-432 ◽  
Author(s):  
Imre Kovesdi ◽  
Tibor Bakacs

: Viral interference, originally, referred to a state of temporary immunity, is a state whereby infection with a virus limits replication or production of a second infecting virus. However, replication of a second virus could also be dominant over the first virus. In fact, dominance can alternate between the two viruses. Expression of type I interferon genes is many times upregulated in infected epithelial cells. Since the interferon system can control most, if not all, virus infections in the absence of adaptive immunity, it was proposed that viral induction of a nonspecific localized temporary state of immunity may provide a strategy to control viral infections. Clinical observations also support such a theory, which gave credence to the development of superinfection therapy (SIT). SIT is an innovative therapeutic approach where a non-pathogenic virus is used to infect patients harboring a pathogenic virus. : For the functional cure of persistent viral infections and for the development of broad- spectrum antivirals against emerging viruses a paradigm shift was recently proposed. Instead of the virus, the therapy should be directed at the host. Such a host-directed-therapy (HDT) strategy could be the activation of endogenous innate immune response via toll-like receptors (TLRs). Superinfection therapy is such a host-directed-therapy, which has been validated in patients infected with two completely different viruses, the hepatitis B (DNA), and hepatitis C (RNA) viruses. SIT exerts post-infection interference via the constant presence of an attenuated non-pathogenic avian double- stranded (ds) RNA viral vector which boosts the endogenous innate (IFN) response. SIT could, therefore, be developed into a biological platform for a new “one drug, multiple bugs” broad-spectrum antiviral treatment approach.


2020 ◽  
Vol 8 (1) ◽  
pp. 85 ◽  
Author(s):  
Sarah D’Alessandro ◽  
Diletta Scaccabarozzi ◽  
Lucia Signorini ◽  
Federica Perego ◽  
Denise P. Ilboudo ◽  
...  

In recent decades, drugs used to treat malaria infection have been shown to be beneficial for many other diseases, including viral infections. In particular, they have received special attention due to the lack of effective antiviral drugs against new emerging viruses (i.e., HIV, dengue virus, chikungunya virus, Ebola virus, etc.) or against classic infections due to drug-resistant viral strains (i.e., human cytomegalovirus). Here, we reviewed the in vitro/in vivo and clinical studies conducted to evaluate the antiviral activities of four classes of antimalarial drugs: Artemisinin derivatives, aryl-aminoalcohols, aminoquinolines, and antimicrobial drugs.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Lin-Lin Ma ◽  
Miao Ge ◽  
Hui-Qiang Wang ◽  
Jin-Qiu Yin ◽  
Jian-Dong Jiang ◽  
...  

Influenza is still a serious threat to human health with significant morbidity and mortality. The emergence of drug-resistant influenza viruses poses a great challenge to existing antiviral drugs. Traditional Chinese medicines (TCMs) may be an alternative to overcome the challenge. Here, 10 oral proprietary Chinese medicines were selected to evaluate their anti-influenza activities. These drugs exhibit potent inhibitory effects against influenza A H1N1, influenza A H3N2, and influenza B virus. Importantly, they demonstrate potent antiviral activities against drug-resistant strains. In the study of mechanisms, we found that Xiaoqinglong mixture could increase antiviral interferon production by activating p38 MAPK, JNK/SAPK pathway, and relative nuclear transcription factors. Lastly, our studies also indicate that some of these medicines show inhibitory activities against EV71 and CVB strains. In conclusion, the 10 traditional Chinese medicines, as kind of compound combination medicines, show broad-spectrum antiviral activities, possibly also including inhibitory activities against strains resistant to available antiviral drugs.


Author(s):  
Dorothy H. Crawford

The term ‘emerging virus infection’ refers to both the emergence of an infectious disease caused by a virus that is new to the species it infects, and to a re-emerging infection, meaning that the disease is increasing in frequency, either in its traditional geographic location or in a new area. ‘Emerging viruses: vertebrate-transmitted viruses’ discusses examples such as swine flu, bird flu, Ebola virus, HIV, and the SARS and MERS coronaviruses. The differing patterns of emerging virus outbreaks depend on viral factors, including incubation period, disease manifestations and method of spread, and important host factors like living conditions, propensity to travel, and the success of any preventive measures.


Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 542 ◽  
Author(s):  
Claudia Claus ◽  
Matthias Jung ◽  
Judith M. Hübschen

The rubella virus (RV) was the first virus shown to be teratogenic in humans. The wealth of data on the clinical symptoms associated with congenital rubella syndrome is in stark contrast to an incomplete understanding of the forces leading to the teratogenic alterations in humans. This applies not only to RV, but also to congenital viral infections in general and includes (1) the mode of vertical transmission, even at early gestation, (2) the possible involvement of inflammation as a consequence of an activated innate immune response, and (3) the underlying molecular and cellular alterations. With the progress made in the development of pluripotent stem cell-based models including organoids and embryoids, it is now possible to assess congenital virus infections on a mechanistic level. Moreover, antiviral treatment options can be validated, and newly emerging viruses with a potential impact on human embryonal development, such as that recently reflected by the Zika virus (ZIKV), can be characterized. Here, we discuss human cytomegalovirus (HCMV) and ZIKV in comparison to RV as viruses with well-known congenital pathologies and highlight their analysis on current models for the early phase of human development. This includes the implications of their genetic variability and, as such, virus strain-specific properties for their use as archetype models for congenital virus infections. In this review, we will discuss the use of induced pluripotent stem cells (iPSC) and derived organoid systems for the study of congenital virus infections with a focus on their prominent aetiologies, HCMV, ZIKV, and RV. Their assessment on these models will provide valuable information on how human development is impaired by virus infections; it will also add new insights into the normal progression of human development through the analysis of developmental pathways in the context of virus-induced alterations. These are exciting perspectives for both developmental biology and congenital virology.


Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2508
Author(s):  
Ruben Soto-Acosta ◽  
Tiffany C. Edwards ◽  
Christine D. Dreis ◽  
Venkatramana D. Krishna ◽  
Maxim C-J. Cheeran ◽  
...  

Broad-spectrum antiviral therapies hold promise as a first-line defense against emerging viruses by blunting illness severity and spread until vaccines and virus-specific antivirals are developed. The nucleobase favipiravir, often discussed as a broad-spectrum inhibitor, was not effective in recent clinical trials involving patients infected with Ebola virus or SARS-CoV-2. A drawback of favipiravir use is its rapid clearance before conversion to its active nucleoside-5′-triphosphate form. In this work, we report a synergistic reduction of flavivirus (dengue, Zika), orthomyxovirus (influenza A), and coronavirus (HCoV-OC43 and SARS-CoV-2) replication when the nucleobases favipiravir or T-1105 were combined with the antimetabolite 6-methylmercaptopurine riboside (6MMPr). The 6MMPr/T-1105 combination increased the C-U and G-A mutation frequency compared to treatment with T-1105 or 6MMPr alone. A further analysis revealed that the 6MMPr/T-1105 co-treatment reduced cellular purine nucleotide triphosphate synthesis and increased conversion of the antiviral nucleobase to its nucleoside-5′-monophosphate, -diphosphate, and -triphosphate forms. The 6MMPr co-treatment specifically increased production of the active antiviral form of the nucleobases (but not corresponding nucleosides) while also reducing levels of competing cellular NTPs to produce the synergistic effect. This in-depth work establishes a foundation for development of small molecules as possible co-treatments with nucleobases like favipiravir in response to emerging RNA virus infections.


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