Status presens of antiviral drugs and strategies: Part II: RNA VIRUSES (EXCEPT RETROVIRUSES)

SARS-CoV-2, EBOV and emerging RNA viruses are amongst the most important global health threats; yet clinically approved antiviral drugs are available for only 10 of the more than 220 viruses known to infect humans.

Download Full-text

4′-Fluorouridine is an oral antiviral that blocks respiratory syncytial virus and SARS-CoV-2 replication

Science ◽

10.1126/science.abj5508 ◽

2022 ◽

Vol 375 (6577) ◽

pp. 161-167

Author(s):

Julien Sourimant ◽

Carolin M. Lieber ◽

Megha Aggarwal ◽

Robert M. Cox ◽

Josef D. Wolf ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Severe Acute Respiratory Syndrome ◽

Broad Spectrum ◽

Rna Viruses ◽

Antiviral Drugs ◽

Emerging Pathogens ◽

Primary Indication ◽

Syncytial Virus ◽

Derivatives Of

Preparing antiviral defenses Antiviral drugs are an important tool in the battle against COVID-19. Both remdesivir and molnupiravir, which target the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase, were first developed against other RNA viruses. This highlights the importance of broad-spectrum antivirals that can be rapidly deployed against related emerging pathogens. Sourimant et al . used respiratory syncytial virus (RSV) as a primary indication in identifying further drugs that target the polymerase enzyme of RNA viruses. The authors explored derivatives of molnupiravir and identified 4′ fluorouridine (EIDD-2749) as an inhibitor of the polymerase of RSV and SARS-CoV-2. This drug can be delivered orally and was effective against RSV in mice and SARS-CoV-2 in ferrets. —VV

Download Full-text

Antiviral Effects of Plant Extracts Used in the Treatment of Important Animal Viral Diseases

World s Veterinary Journal ◽

10.54203/scil.2021.wvj67 ◽

2021 ◽

Vol 11 (4) ◽

pp. 521-533

Author(s):

Gamil Sayed Gamil Zeedan ◽

Abeer Mostafa Abdalhamed

Keyword(s):

Antiviral Activity ◽

Viral Infection ◽

Plant Extracts ◽

Rna Viruses ◽

Biological Activities ◽

Antiviral Drugs ◽

Antiviral Compounds ◽

Antiviral Activities

The goal of this review was to highlight some plant species that have significant antiviral activity against DNA and RNA viruses in vitro and in vivo although more research is needed to address safety issues, drug interactions, and the possibility of using them in combination with other natural products. Viral infection plays an important role in human and animal diseases. Although there have been advances in immunization and antiviral drugs, there is still a lack of protective vaccines and effective antiviral drugs in human and veterinary medicine. The lack of effective antivirals necessitates the search for new effective antiviral compounds. Plants are naturally gifted at synthesizing antiviral compounds. They are rich sources of phytochemicals with different biological activities, including antiviral activities as a result of advanced analytical chemistry, standard virus assays, and development of standardization and extraction methods. Plant extracts have a wide variety of active compounds, including flavonoids, terpenoids, lignans, sulphides, polyphenolics, coumarins, saponins, furyl compounds, alkaloids, polyines, thiophenes, proteins, and peptides. Moreover, certain volatile oils have indicated a high level of antiviral activity. Replication, assembly, and release, as well as targeting virus host-specific interactions capable of inhibiting several viruses, could help the development of broad-spectrum antivirals for the prevention and control of viral pathogens. The in vitro antiviral activities of Erythroxylum deciduum, Lacistema hasslerianum (chodat), Xylopia aromatica, Heteropteris aphrodisiaca, Acacia nilotica (gum arabic tree), Lippia graveolens (Guettarda angelica (Velvetseed), Prunus myrtifolia, and Symphyopappus plant extracts can inhibite viral replication, and interfer with the early stages of viral adsorption of DNA viruses. However, Boesenbergia rotunda plant extracts have inhibited RNA viruses. A potent anti-SARS-CoV-2 inhibitor with B. rotunda extract and panduratin A after viral infection drastically suppresses SARS-CoV-2 infectivity in Vero E6 cells.

Download Full-text

Antiviral activity of Glucosylceramide synthase inhibitors against SARS-CoV-2 and other RNA virus infections

10.1101/2020.05.18.103283 ◽

2020 ◽

Cited By ~ 2

Author(s):

Einat. B. Vitner ◽

Roy Avraham ◽

Hagit Achdout ◽

Hadas Tamir ◽

Avi Agami ◽

...

Keyword(s):

Broad Spectrum ◽

Influenza A ◽

Cell Membranes ◽

Rna Viruses ◽

Rna Virus ◽

Antiviral Drugs ◽

Membrane Dynamics ◽

Biologically Active ◽

Phase Iii ◽

Glucosylceramide Synthase

AbstractThe need for antiviral drugs is real and relevant. Broad spectrum antiviral drugs have a particular advantage when dealing with rapid disease outbreaks, such as the current COVID-19 pandemic. Since viruses are completely dependent on internal cell mechanisms, they must cross cell membranes during their lifecycle, creating a dependence on processes involving membrane dynamics. Thus, in this study we examined whether the synthesis of glycosphingolipids, biologically active components of cell membranes, can serve as an antiviral therapeutic target. We examined the antiviral effect of two specific inhibitors of GlucosylCeramide synthase (GCS); (i) Genz-123346, an analogue of the FDA-approved drug Cerdelga®, (ii) GENZ-667161, an analogue of venglustat which is currently under phase III clinical trials. We found that both GCS inhibitors inhibit the replication of four different enveloped RNA viruses of different genus, organ-target and transmission route: (i) Neuroinvasive Sindbis virus (SVNI), (ii) West Nile virus (WNV), (iii) Influenza A virus, and (iv) SARS-CoV-2. Moreover, GCS inhibitors significantly increase the survival rate of SVNI-infected mice. Our data suggest that GCS inhibitors can potentially serve as a broad-spectrum antiviral therapy and should be further examined in preclinical and clinical trial. Analogues of the specific compounds tested have already been studied clinically, implying they can be fast-tracked for public use. With the current COVID-19 pandemic, this may be particularly relevant to SARS-CoV-2 infection.One Sentence SummaryAn analogue of Cerdelga®, an FDA-approved drug, is effective against a broad range of RNA-viruses including the newly emerging SARS-CoV-2.

Download Full-text

Predicting Broad-Spectrum Antiviral Drugs against RNA Viruses Using Transcriptional Responses to Exogenous RNA

10.20944/preprints202003.0437.v2 ◽

2021 ◽

Author(s):

Akpeli V. Nordor ◽

Geoffrey H. Siwo

Keyword(s):

Antiviral Activity ◽

Small Molecules ◽

Broad Spectrum ◽

Rna Viruses ◽

Antiviral Drugs ◽

Viral Rna ◽

Host Cells ◽

Target Cells ◽

Transcriptional Responses ◽

Exogenous Rna

All RNA viruses deliver their genomes into target host cells through processes distinct from normal trafficking of cellular RNA transcripts. The delivery of viral RNA into most cells hence triggers innate antiviral defenses that recognize viral RNA as foreign. In turn, viruses have evolved mechanisms to subvert these defenses, allowing them to thrive in target cells. Therefore, drugs activating defense to exogenous RNA could serve as broad-spectrum antiviral drugs. Here we show that transcriptional signatures associated with cellular responses to the delivery of a non-viral exogenous RNA sequence into human cells predict small molecules with broad-spectrum antiviral activity. In particular, transcriptional responses to the delivery of Cas9 mRNA into human hematopoietic stem and progenitor cells (HSPCs) highly matches those triggered by small molecules with broad-spectrum antiviral activity such as emetine, homoharringtonine, pyrvinium pamoate and anisomycin, indicating that these drugs are potentially active against other RNA viruses. Furthermore, these drugs have been approved for other indications and could thereby be repurposed to novel viruses. We propose that the antiviral activity of these drugs to SARS-CoV-2 should therefore be determined as they have been shown as active against other coronaviruses including SARS-CoV-1 and MERS-CoV. Indeed, two of these drugs- emetine and homoharringtonine- were independently shown to inhibit SARS-CoV-2 as this article was in preparation. These drugs could also be explored as potential adjuvants to COVID-19 vaccines in development due to their potential effect on the innate antiviral defenses that could bolster adaptive immunity when delivered alongside vaccine antigens.

Download Full-text

Predicting Broad-Spectrum Antiviral Drugs against RNA Viruses Using Transcriptional Responses to Exogenous RNA

10.20944/preprints202003.0437.v1 ◽

2020 ◽

Author(s):

Akpeli V. Nordor ◽

Geoffrey H. Siwo

Keyword(s):

Antiviral Activity ◽

Small Molecules ◽

Broad Spectrum ◽

Rna Viruses ◽

Antiviral Drugs ◽

Viral Rna ◽

Host Cells ◽

Target Cells ◽

Transcriptional Responses ◽

Exogenous Rna

All RNA viruses deliver their genomes into target host cells through processes distinct from normal trafficking of cellular RNA transcripts. The delivery of viral RNA into most cells hence triggers innate antiviral defenses that recognize viral RNA as foreign. In turn, viruses have evolved mechanisms to subvert these defenses, allowing them to thrive in target cells. Therefore, drugs activating defense to foreign or exogenous RNA could serve as broad-spectrum antiviral drugs. Here we show that transcriptional signatures associated with cellular responses to the delivery of a non-viral exogenous RNA sequence into human cells predicts small molecules with broad-spectrum antiviral activity. In particular, transcriptional responses to the delivery of cas9 mRNA into human hematopoietic stem and progenitor cells (HSPCs) highly matches those triggered by small molecules with broad-spectrum antiviral activity such as emetine, homoharringtonine, pyrvinium pamoate and anisomycin, indicating that these drugs are potentially active against other RNA viruses. Furthermore, these drugs have been approved for other indications and could thereby be repurposed to novel viruses. We propose that the antiviral activity of these drugs to SARS-CoV-2 should therefore be determined as they have been shown as active against other coronaviruses including SARS-CoV and MERS-CoV. These drugs could also be explored as potential adjuvants to COVID-19 vaccines in development due to their potential effect on the innate antiviral defenses that could bolster adaptive immunity when delivered alongside vaccine antigens.

Download Full-text

Long Short-Term Memory Neural Networks for RNA Viruses Mutations Prediction

Mathematical Problems in Engineering ◽

10.1155/2021/9980347 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Takwa Mohamed ◽

Sabah Sayed ◽

Akram Salah ◽

Essam H. Houssein

Keyword(s):

Neural Network ◽

Language Processing ◽

Short Term Memory ◽

Rna Viruses ◽

Antiviral Drugs ◽

Rna Sequences ◽

Text Data ◽

Dna And Rna ◽

Proposed Model ◽

Drug Resistant Strains

Viral progress remains a major deterrent in the viability of antiviral drugs. The ability to anticipate this development will provide assistance in the early detection of drug-resistant strains and may encourage antiviral drugs to be the most effective plan. In recent years, a deep learning model called the seq2seq neural network has emerged and has been widely used in natural language processing. In this research, we borrow this approach for predicting next generation sequences using the seq2seq LSTM neural network while considering these sequences as text data. We used hot single vectors to represent the sequences as input to the model; subsequently, it maintains the basic information position of each nucleotide in the sequences. Two RNA viruses sequence datasets are used to evaluate the proposed model which achieved encouraging results. The achieved results illustrate the potential for utilizing the LSTM neural network for DNA and RNA sequences in solving other sequencing issues in bioinformatics.

Download Full-text

Oncogenesis and the Lucké Virus

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100743 ◽

1968 ◽

Vol 26 ◽

pp. 200-201

Author(s):

A. E. Vatter ◽

J. Zambernard

Keyword(s):

Rna Viruses ◽

Vegetative State ◽

Temperature Sensitive ◽

Structural Level ◽

Oncogenic Viruses ◽

Dna Viruses ◽

Leopard Frogs ◽

Renal Adenocarcinoma ◽

Induced Tumors ◽

Northern Leopard Frogs

Oncogenic viruses, like viruses in general, can be divided into two classes, those that contain deoxyribonucleic acid (DNA) and those that contain ribonucleic acid (RNA). The RNA viruses have been recovered readily from the tumors which they cause whereas, the DNA-virus induced tumors have not yielded the virus. Since DNA viruses cannot be recovered, the bulk of present day investigations have been concerned with RNA viruses.The Lucké renal adenocarcinoma is a spontaneous tumor which occurs in northern leopard frogs (Rana pipiens) and has received increased attention in recent years because of its probable viral etiology. This hypothesis was first advanced by Lucké after he observed intranuclear inclusions in some of the tumor cells. Tumors with inclusions were examined at the fine structural level by Fawcett who showed that they contained immature and mature virus˗like particles.The use of this system in the study of oncogenic tumors offers several unique features, the virus has been shown to contain DNA and it can be recovered from the tumor, also, it is temperature sensitive. This latter feature is of importance because the virus can be transformed from a latent to a vegetative state by lowering or elevating the environmental temperature.

Download Full-text