An Overview of Natural and Synthetic Analogs of Quinoline for the Prophylaxis of COVID-19. Chloroquine Analogs: An Overview of Natural and Synthetic Quinolines as Broad Spectrum Antiviral Agents

2020 ◽  
Vol 26 ◽  
Author(s):  
Veera Bramhachari Pallaval ◽  
Manasa Kanithi ◽  
Sangeetha Meenakshisundaram ◽  
Achanta Jagadeesh ◽  
Mattareddy Alavala ◽  
...  
Keyword(s):  
Viral Entry ◽  
Broad Spectrum ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Host Immune System ◽  
Area Of Interest ◽  
Post Entry ◽  
Synthetic Derivatives ◽  
Potential Area ◽  
Natural And Synthetic

: SARS-CoV-2, a positive single-stranded RNA enveloped coronavirus, currently poses a global health threat. Drugs with quinoline scaffolds have long been studied to repurpose their useful broad-spectrum properties into treating various diseases, including viruses. Preliminary studies on the quinoline medications, Chloroquine and Hydroxy chloroquine, against SARS-CoV2, have shown to be a potential area of interest for drug development, due to their ability to prevent viral entry, act as anti-inflammatory modulators, and inhibit key enzymes allowing reduced viral infectivity. In addition to Chloroquine and Hydroxychloroquine, we discuss analogs of the drugs to understand the quinoline scaffold’s potential antiviral mechanisms. The heterocyclic scaffold of quinoline can be modified in many ways primarily through the modification of its substituents, we cover these different synthetic derivatives to understand properties that could enhance its antiviral specificity thoroughly. Chloroquine and its analogs can act on various stages of the viral life cycle pre and post entry. In this study, we review Chloroquine and its synthetic and natural analogs for their antiviral properties in a variety of different viruses. Furthermore, we review the compound’s potential abilities to attenuate symptoms associated with viral infections. Natural compounds that share scaffolding to Chloroquine can act as antivirals or attenuate symptoms through stimulate the host immune system or reducing oxidative stress. Furthermore, we discuss perspectives of the drug’s repurposing due to its ability to inhibit beta-hematin formation and to be a Zinc Ionophore.

scholarly journals Nanobiocide Based-Silver Nanomaterials Upon Coronaviruses: Approaches for Preventing Viral Infections

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Kamyar Khoshnevisan ◽  
Hassan Maleki ◽  
Hadi Baharifar
Keyword(s):  
Viral Entry ◽  
Viral Infections ◽  
Respiratory Infections ◽  
Antiviral Agents ◽  
Long Term Stability ◽  
Silver Nanomaterials ◽  
Inhibitory Mechanisms ◽  
Low Toxicity ◽  
Nano Graphene

Abstract The effectiveness of silver nanomaterials (AgNMs), as antiviral agents, has been confirmed in humans against many different types of viruses. Nanobiocides-based AgNMs can be effectively applied to eliminate coronaviruses (CoVs), as the cause of various diseases in animals and humans, particularly the fatal human respiratory infections. Mostly, these NMs act effectively against CoVs, thanks to the NMs’ fundamental anti-viral structures like reactive oxygen species (ROS), and photo-dynamic and photo-thermal abilities. Particularly, the antiviral activity of AgNMs is clarified under three inhibitory mechanisms including viral entry limitation, attachment inhibition, and viral replication limitation. It is believed that nanobiocide with other possible materials such as TiO2, silica and, carbon NMs exclusively nano-graphene materials can emerge as a more effective disinfectant for long-term stability with low toxicity than common disinfectants. Nanobiocides also can be applied for the prevention and treatment of viral infections specifically against COVID-19. Graphic Abstract

scholarly journals NAD+-consuming enzymes in immune defense against viral infection

2021 ◽  
Vol 478 (23) ◽  
pp. 4071-4092
Author(s):  
Jialin Shang ◽  
Michael R. Smith ◽  
Ananya Anmangandla ◽  
Hening Lin
Keyword(s):  
Immune Responses ◽  
Broad Spectrum ◽  
Defense Mechanisms ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Scientific Progress ◽  
Immune Defense ◽  
Past Century ◽  
Antiviral Immune Response ◽  
Antiviral Function

The COVID-19 pandemic reminds us that in spite of the scientific progress in the past century, there is a lack of general antiviral strategies. In analogy to broad-spectrum antibiotics as antibacterial agents, developing broad spectrum antiviral agents would buy us time for the development of vaccines and treatments for future viral infections. In addition to targeting viral factors, a possible strategy is to understand host immune defense mechanisms and develop methods to boost the antiviral immune response. Here we summarize the role of NAD+-consuming enzymes in the immune defense against viral infections, with the hope that a better understanding of this process could help to develop better antiviral therapeutics targeting these enzymes. These NAD+-consuming enzymes include PARPs, sirtuins, CD38, and SARM1. Among these, the antiviral function of PARPs is particularly important and will be a focus of this review. Interestingly, NAD+ biosynthetic enzymes are also implicated in immune responses. In addition, many viruses, including SARS-CoV-2 contain a macrodomain-containing protein (NSP3 in SARS-CoV-2), which serves to counteract the antiviral function of host PARPs. Therefore, NAD+ and NAD+-consuming enzymes play crucial roles in immune responses against viral infections and detailed mechanistic understandings in the future will likely facilitate the development of general antiviral strategies.

scholarly journals Superinfection Exclusion of Alphaherpesviruses Interferes with Virion Trafficking

2021 ◽  
Author(s):  
Matthew Pendleton Taylor ◽  
James Patrick Cwick ◽  
Jonathan Owen ◽  
Irina Kotchetkova ◽  
Nick Van Horssen
Keyword(s):  
Viral Entry ◽  
Pseudorabies Virus ◽  
Fluorescent Protein ◽  
Viral Infections ◽  
Fluorescent Microscopy ◽  
Receptor Expression ◽  
Superinfection Exclusion ◽  
Post Entry ◽  
Simplex Virus ◽  
Hsv 1

Superinfection exclusion (SIE) is a phenomenon in which a primary viral infection interferes with secondary viral infections within that same cell. Although SIE has been observed across many viruses, it has remained relatively understudied. A recently characterized glycoprotein D (gD) -independent SIE of alphaherpesviruses presents a novel mechanism of co-infection restriction for Herpes Simplex Virus Type 1 (HSV-1) and Pseudorabies virus (PRV). In this study, we evaluated the role of multiplicity of infection (MOI), receptor expression, and trafficking of virions to gain greater insight into potential mechanisms of alphaherpesvirus SIE. We observed that high MOI secondary viral infections were able to overcome SIE in a manner that was independent of receptor availability. Utilizing recombinant viruses expressing fluorescent protein fusions, we assessed virion localization during SIE through live fluorescent microscopy of dual-labeled virions and localization of capsid assemblies. Analysis of these assemblies confirmed changes in the distribution of capsids during SIE. These results indicate that SIE during PRV infection inhibits viral entry or fusion while HSV-1 SIE inhibits infection through a post-entry mechanism. Although the timing and phenotype of SIE is similar between alphaherpesviruses, the related viruses implement different mechanisms to restrict coinfection.

scholarly journals Antiviral Compounds from Myxobacteria

2018 ◽  
Vol 6 (3) ◽  
pp. 73 ◽  
Author(s):  
Lucky Mulwa ◽  
Marc Stadler
Keyword(s):  
Broad Spectrum ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Public Health Issue ◽  
Target Cells ◽  
Global Public Health ◽  
Drug Candidates ◽  
Antiviral Compounds ◽  
Spectrum Activity

Viral infections including human immunodeficiency virus (HIV), cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV) pose an ongoing threat to human health due to the lack of effective therapeutic agents. The re-emergence of old viral diseases such as the recent Ebola outbreaks in West Africa represents a global public health issue. Drug resistance and toxicity to target cells are the major challenges for the current antiviral agents. Therefore, there is a need for identifying agents with novel modes of action and improved efficacy. Viral-based illnesses are further aggravated by co-infections, such as an HIV patient co-infected with HBV or HCV. The drugs used to treat or manage HIV tend to increase the pathogenesis of HBV and HCV. Hence, novel antiviral drug candidates should ideally have broad-spectrum activity and no negative drug-drug interactions. Myxobacteria are in the focus of this review since they produce numerous structurally and functionally unique bioactive compounds, which have only recently been screened for antiviral effects. This research has already led to some interesting findings, including the discovery of several candidate compounds with broad-spectrum antiviral activity. The present review looks at myxobacteria-derived antiviral secondary metabolites.

scholarly journals Development of Broad-Spectrum Antiviral Agents—Inspiration from Immunomodulatory Natural Products

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1257
Author(s):  
Mengxun Zhang ◽  
Jiaqing Zhong ◽  
Yongai Xiong ◽  
Xun Song ◽  
Chenyang Li ◽  
...  
Keyword(s):  
Natural Products ◽  
Broad Spectrum ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Antiviral Drugs ◽  
Life Cycles ◽  
The Body ◽  
Host Cells ◽  
Immunomodulatory Effects ◽  
Antiviral Effects

Developing broad-spectrum antiviral drugs remains an important issue as viral infections continue to threaten public health. Host-directed therapy is a method that focuses on potential targets in host cells or the body, instead of viral proteins. Its antiviral effects are achieved by disturbing the life cycles of pathogens or modulating immunity. In this review, we focus on the development of broad-spectrum antiviral drugs that enhance the immune response. Some natural products present antiviral effects mediated by enhancing immunity, and their structures and mechanisms are summarized here. Natural products with immunomodulatory effects are also discussed, although their antiviral effects remain unknown. Given the power of immunity and the feasibility of host-directed therapy, we argue that both of these categories of natural products provide clues that may be beneficial for the discovery of broad-spectrum antiviral drugs.

scholarly journals The Broad-Spectrum Antiviral Potential of the Amphibian Peptide AR-23

2022 ◽  
Vol 23 (2) ◽  
pp. 883
Author(s):  
Annalisa Chianese ◽  
Carla Zannella ◽  
Alessandra Monti ◽  
Anna De Filippis ◽  
Nunzianna Doti ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Broad Spectrum ◽  
Viral Infections ◽  
Antiviral Agents ◽  
World Population ◽  
Therapeutic Effects ◽  
Amphibian Skin ◽  
Antibacterial And Antifungal Activities ◽  
Dna And Rna ◽  
Antibacterial And Antifungal

Viral infections represent a serious threat to the world population and are becoming more frequent. The search and identification of broad-spectrum antiviral molecules is necessary to ensure new therapeutic options, since there is a limited availability of effective antiviral drugs able to eradicate viral infections, and consequently due to the increase of strains that are resistant to the most used drugs. Recently, several studies on antimicrobial peptides identified them as promising antiviral agents. In detail, amphibian skin secretions serve as a rich source of natural antimicrobial peptides. Their antibacterial and antifungal activities have been widely reported, but their exploitation as potential antiviral agents have yet to be fully investigated. In the present study, the antiviral activity of the peptide derived from the secretion of Rana tagoi, named AR-23, was evaluated against both DNA and RNA viruses, with or without envelope. Different assays were performed to identify in which step of the infectious cycle the peptide could act. AR-23 exhibited a greater inhibitory activity in the early stages of infection against both DNA (HSV-1) and RNA (MeV, HPIV-2, HCoV-229E, and SARS-CoV-2) enveloped viruses and, on the contrary, it was inactive against naked viruses (PV-1). Altogether, the results indicated AR-23 as a peptide with potential therapeutic effects against a wide variety of human viruses.

scholarly journals Discovery and Development of Safe-in-Man Broad-Spectrum Antiviral Agents

2020 ◽  
Author(s):  
Petter I. Andersen ◽  
Aleksandr Ianevski ◽  
Hilde Lysvand ◽  
Astra Vitkauskiene ◽  
Valentyn Oksenych ◽  
...  
Keyword(s):  
General Population ◽  
Broad Spectrum ◽  
Clinical Studies ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Viral Diseases ◽  
The World ◽  
Additional Protection ◽  
Emerging Viral Diseases ◽  
World Virus

Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs) could provide additional protection of general population from emerging and re-emerging viral diseases reinforcing the arsenal of available antiviral options. Here, we reviewed discovery and development of BSAAs and summarized the information on 119 safe-in-man agents in freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections.

scholarly journals Discovery and Development of Safe-in-Man Broad-Spectrum Antiviral Agents

2020 ◽  
Author(s):  
Petter I. Andersen ◽  
Aleksandr Ianevski ◽  
Hilde Lysvand ◽  
Astra Vitkauskiene ◽  
Valentyn Oksenych ◽  
...  
Keyword(s):  
General Population ◽  
Broad Spectrum ◽  
Clinical Studies ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Viral Diseases ◽  
The World ◽  
Additional Protection ◽  
Emerging Viral Diseases ◽  
World Virus

Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of general population from emerging and re-emerging viral diseases reinforcing the arsenal of available antiviral options. Here, we reviewed discovery and development of BSAAs and summarized the information on 120 safe-in-man agents in freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections.

scholarly journals Discovery and Development of Safe-in-Man Broad-Spectrum Antiviral Agents

2020 ◽  
Author(s):  
Petter I. Andersen ◽  
Aleksandr Ianevski ◽  
Hilde Lysvand ◽  
Astra Vitkauskiene ◽  
Valentyn Oksenych ◽  
...  
Keyword(s):  
General Population ◽  
Broad Spectrum ◽  
Clinical Studies ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Viral Diseases ◽  
The World ◽  
Additional Protection ◽  
Emerging Viral Diseases ◽  
World Virus

Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of general population from emerging and re-emerging viral diseases reinforcing the arsenal of available antiviral options. Here, we reviewed discovery and development of BSAAs and summarized the information on 120 safe-in-man agents in freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections.

Therapeutic Exploitation of Viral Interference

2020 ◽  
Vol 20 (4) ◽  
pp. 423-432 ◽  
Author(s):  
Imre Kovesdi ◽  
Tibor Bakacs
Keyword(s):  
Broad Spectrum ◽  
Viral Infections ◽  
Viral Vector ◽  
Antiviral Treatment ◽  
Type I ◽  
Virus Infections ◽  
Emerging Viruses ◽  
Viral Interference ◽  
Pathogenic Virus ◽  
Hepatitis C Rna

: 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.

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