Get Permission Kumar, Kumar, Kumar, Jha, Tiwari, and Gupta: Important antiviral properties of Streptomyces species compounds


Introduction

The investigation natural compounds from Streptomyces species; a subgroup of Actinomycetes bacteria, for antiviral properties offers a possible way to combat viral infections. Streptomyces species produce various bioactive secondary metabolites, some of which have antiviral effects.1 These microbial metabolites offer a promising opportunity for new antiviral therapeutics against a variety of viral infections. Several Streptomyces species produce bioactive secondary metabolites that exhibit a broad spectrum of chemical structures and potent biological activity. These chemicals show potential for fighting viral infections by targeting various stages of viral replication or interactions with host cells.2 These metabolites, with their various chemical structures and biological activity, present promising pathways for the creation of new antiviral treatments. Harnessing the antiviral capability of Streptomyces-derived chemicals is a huge step forward in the ongoing battle against viral infections, underscoring the necessity of looking to natural sources for novel solutions to global health problems.3 The antiviral properties of these metabolites make them important for biological research and pharmaceutical development. These chemicals are promising in the fight against influenza viruses, herpes viruses and HIV by targeting viral replication or interactions between host cells. Streptomyces species produce bioactive secondary metabolites that are not only of biomedical, but also of economic and industrial use.4, 5 The diverse chemical compositions and potent biological properties of Actinomycetes have applications in pharmacy, agriculture and biotechnology, all of which aim to improve human health and well-being by utilizing microbial diversity. Actinomycetes are therefore important partners in humanity's ongoing endeavors’ to harness the potential of microbial ecosystems for societal progress. The use of actinomycete-derived molecules emphasizes their central role in various fields and highlights their indispensable contribution to the search for solutions that benefit both human well-being and global progress.6 Streptomyces species are known for their ability to synthesise a wide range of natural products that exhibit remarkable structural diversity. These compounds include macrolides, tetracyclines, aminoglycosides, glycopeptides, ansamycins and terpenes.7, 8 Streptomyces hygroscopicus in particular stands out as an outstanding producer, secreting around 180 metabolites with different bioactivities. These metabolites hold immense potential for various applications in medicine, agriculture and industry and contribute to advances in drug development, agricultural solutions and industrial processes.9 Current research highlights the importance of Streptomyces as a source of bioactive chemicals and their potential to improve human health by tapping into the chemical diversity found in nature.

Streptomyces as a Natural Healer

Streptomyces bacteria stand out as natural healers, possessing a remarkable ability to produce bioactive compounds with therapeutic potential. These microorganisms have garnered attention for their diverse repertoire of secondary metabolites, many of which exhibit powerful medicinal properties. Streptomyces-derived compounds have been instrumental in the development of numerous antibiotics, such as streptomycin and erythromycin, which have revolutionized the treatment of bacterial infections.10 Beyond antibiotics, Streptomyces metabolites also demonstrate activity against other pathogens, including viruses and fungi, making them valuable candidates for antiviral and antifungal therapies. Moreover, these bioactive compounds hold promise in combating cancer, inflammation, and other complex diseases, showcasing the versatility of Streptomyces in medical research. By tapping into the natural capabilities of Streptomyces, researchers continue to uncover novel therapeutic agents with diverse mechanisms of action and improved efficacy. As such, Streptomyces emerges not only as a natural healer but also as a source of inspiration for the development of innovative medicines to address a wide range of health challenges.8, 11 Streptomyces bacteria show different behaviours when confronted with viral infections, demonstrating their exceptional adaptability and defensive capabilities. These chemicals can interfere with various stages of viral replication, such as viral entry, genome replication and assembly, thereby preventing the replication and spread of the virus. In addition, Streptomyces species use sophisticated quorum sensing mechanisms to communicate and coordinate their responses to viral threats (Sarveswari and Solomon, 2019). This communication network allows them to alter their gene expression and metabolic processes in real time, enhancing their ability to fight viral infections.

Streptomyces bacteria can also influence the host's immune response to viral infections and thus possibly strengthen the host's defences against invading viruses.5, 8 The bacteria help the host to build a strong antiviral defence by increasing the production of antimicrobial peptides, enhancing phagocytosis and controlling the production of cytokines. They compete with viruses for important nutrients and resources in their environment. The bacteria have potential to reduce the viral load in their environment by competing with viruses for these nutrients.11, 12 They may also have built-in or learned methods to fight viral infections, such as restriction modification systems, CRISPR-Cas systems or the production of viral defence proteins. These processes provide additional layers of defence against viral threats and demonstrate the plasticity and tenacity of Streptomyces bacteria in the fight against viral infections. Streptomyces' broad set of behaviours highlights their importance as beneficial friends in the ongoing war against viral infections.3, 13

Potential Antiviral Compounds from Streptomyces

Streptomyces bacteria contain a wealth of potentially antiviral chemicals, including a variety of secondary metabolites that promise efficacy against viral infections. These chemicals, derived from different Streptomyces species, have a variety of mechanisms that target different stages of viral replication or the host cell. Many viruses, including herpesviruses, HIV-1 and influenza A virus, can be killed by compounds derived from Streptomyces.8 These include polyene antibiotics (such as streptovaricins) and cyclic depsipeptides (such as azalomycins).14 Many complex polyketides, such as napyradiomycins, and antibiotics, such as salinomycin, have the potential to prevent viral entry or replication.15 The discovery of these antiviral molecules underscores the need to look to nature for novel drugs, and Streptomyces is emerging as a promising option for the development of new antiviral drugs. Among these compounds are:

Table 1

List of natural compounds and its role against viral pathogens

Compounds

Streptomyces sp.

Role against virus

References

Avilamycin

Streptomyces viridochromogenes

Inhibit the transcription in HIV-1 and other retroviruses

16, 17

Azalomycin

Streptomyces hygroscopicus

These compounds are cyclic depsipeptides show its antiviral activities against Herpes simplex virus (HSV) -1 and -2

18, 19, 20

Herboxidiene

Streptomyces chromofuscus

Inhibits the replication of HIV-1

21, 22

Madumycin

Streptomyces venezuelae

Inhibit the DNA replication in HSV-1

23, 24

Napyradiomycins

Streptomyces kebangsaanensis WS-68302

Blocking the entry of HIV-1 in host cell

25

Nourseothricin

Streptomyces noursei

Inhibiting protein synthesis in adenoviruses, herpesviruses, and poxviruses during infection

26, 27, 28

Salinomycin

Streptomyces albus

Restrict the growth of RNA viruses, including influenza A virus and Zika virus

29, 30

Streptovaricins

Streptomyces griscus

Exhibit antiviral activity against herpes simplex virus (HSV) and vaccinia virus by disrupting viral membrane integrity

31, 32

To fully exploit the potential of these molecules, their mode of action, efficacy and safety profile need to be further investigated the in treating viral infections and addressing global health concerns. The bacteria represent a rich source of potential antiviral compounds, with numerous secondary metabolites showing promising activity against viral infections (Table 1, Figure 1).

Figure 1

Compounds (Table 1)

https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/7b9d5902-3fb6-4ccb-8668-06f952762334/image/c716c4f2-07f4-4157-bbfc-707c56fb3826-uimage.png

Antiviral Mechanism of Secondary Metabolites from Streptomyces

The secondary metabolites of Streptomyces have numerous antiviral mechanisms that inhibit viral infections at different stages of the viral life cycle. Streptomyces-derived secondary metabolites are known to have a broad spectrum of structures and potent biological activity.2 They could be used for the production of new antiviral drugs (Figure 2). Preventing viruses from entering host cells is one of the most important antiviral mechanisms. To prevent viruses from attaching to and entering cells, some secondary metabolites produced by Streptomyces species bind to specific proteins or receptors on their surface. These chemicals block the initial stages of infection where the virus attempts to infect the host cells, preventing the virus from replicating and spreading. They can also target the pathways that the virus uses to replicate in the infected cells. These substances have the potential to block viral enzymes that are essential for processes such as genome replication, transcription and protein synthesis.33 To illustrate, there are Streptomyces compounds that can interfere with the process of viral particle formation by interfering with viral DNA polymerase and RNA-dependent RNA polymerase. This can interfere with viral nucleic acid synthesis. These drugs effectively suppress viral replication and spread and interfere with essential processes of viral replication. These agents not only directly target viral components, but also enhance the host's innate immune response to viral infections through immunomodulatory actions. By acting on antiviral signalling pathways, these chemicals can promote the synthesis of interferons and other antiviral cytokines that inhibit viral replication.34 In addition, certain Streptomyces metabolites increase the phagocytic activity of immune cells, which helps the body to remove virus-infected cells and viral particles. The compounds also cause apoptosis in infected cells.35 These chemicals inhibit the replication and spread of the virus in the host by triggering apoptosis, which eliminates virus-infected cells before viral replication can take place. This process not only eliminates virus-infected cells but also prevents the release of new infectious virus particles. In combination with conventional antiviral drugs, the secondary metabolites obtained from Streptomyces can have additive or synergistic effects.36 This method of combination therapy has the potential to increase antiviral efficacy, reduce drug resistance and increase antiviral activity against a variety of viral infections. The metabolites have a multi-pronged attack against viruses, targeting their entry, replication, immune evasion, survival of infected cells and dissemination. The processes described here show that Streptomyces-derived drugs are promising for new antiviral treatments due to their broad spectrum of activity and low risk of resistance.

Figure 2

Inhibitory mechanism of natural compounds against viral pathogens

https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/deaf7b85-aecb-4dc2-b930-427315d6f203image9.jpeg

Futuristic Prospects of Streptomyces in Viral Infection

Members of the actinomycete class, especially Streptomyces, are often neglected, although the metabolites of many bacterial species are widely studied and used in the treatment of viral infections.37 New research has shown that Streptomyces and other actinomycetes can improve the health of people who are sick with viruses. Streptomyces, whether studied individually or in combination, has been the main focus of previous research. Nevertheless, a number of original studies published recently have highlighted multi-species techniques as important environmentally friendly solutions for infection management. Streptomyces is a bacterial species, but it has the potential to unlock new health benefits and natural chemicals when combined with other bacterial species. A more holistic approach is needed to combat viral infections, and this trend towards using mixtures of different species is bringing to light the untapped potential of actinomycetes in medicine.

Conclusion

Actinomycetes, especially Streptomyces, are usually neglected in the treatment of viral infections, although many bacterial metabolites have been studied. Recent research suggests that combining Streptomyces with other bacterial species could improve overall health and regulate infections. Earlier studies focused on single or multiple Streptomyces strains, while today's work focuses on multiple species. This emphasises the importance of comprehensive approaches to fighting viral infections and exploring natural products. By using actinomycetes in combination therapies, unimagined health benefits can be discovered and environmentally sustainable approaches to treating viral infections can be created. Therefore, it is necessary to conduct further research on multispecies combinations of Streptomyces and other bacterial species to fully exploit their therapeutic potential against viral diseases.

Source of Funding

The authors received no financial support for the research authorship and / or publication of this article.

Conflict of Interest

None

Ethical Clearance

None

Acknowledgment

We are thankful to our Dr. Saurabh Varshney (Sir) Executive Director AIIMS Deoghar for his valuable suggestions and support for this study.

References

1 

K Alam A Mazumder S Sikdar YM Zhao J Hao C Song Streptomyces: The biofactory of secondary metabolitesFront Microbiol202213968053

2 

HJ Lacey PJ Rutledge Recently discovered secondary metabolites from Streptomyces speciesMolecules2022273887

3 

AS Abdel-Razek ME El-Naggar A Allam OM Morsy SI Othman Microbial natural products in drug discoveryProcesses202084470

4 

S Pacios-Michelena CNA González OB Alvarez-Perez R Rodriguez-Herrera M Chávez-González RA Valdés Application of Streptomyces antimicrobial compounds for the control of phytopathogensFront Sustainable Food Syst20215696518

5 

R Salwan V Sharma Bioactive compounds of Streptomyces: biosynthesis to applications. Studies in natural products chemistryStud Natl Prod Chem20206446791

6 

S Adapa S Naramala V Gayam R Kapoor M Raju P Patel An Unusual Presentation From a Sporadic Partially Acid-Fast Aerobic Actinomycete Resistant to Common AntibioticsJ Investig Med High Impact Case Rep202082324709619899598

7 

SK Wrigley MA Hayes R Thomas EJT Chrystal N Nicholson AL Demain PJ Wilson JT Chrystal SK Wrigley R Thomas N Nicholson M Hayes Microbial natural products: a past with a futureNew Leads for the Pharmaceutical and Agrochemical IndustriesThe Royal Society of ChemistryUnited Kingdom2000316

8 

KS Acquah DW Gammon DR Beukes South African actinobacteria: A treasure trove of novel bioactive metabolites for drug discoverySouth Afr J Sci20241201-21

9 

MM Tangerina LC Furtado VM Leite A Bauermeister K Velasco-Alzate PC Jimenez Metabolomic study of marine Streptomyces sp.: Secondary metabolites and the production of potential anticancer compoundsPLoS One20201512e0244385

10 

HM Kemung LT Tan TM Khan KG Chan P Pusparajah BH Goh Streptomyces as a prominent resource of future anti-MRSA drugsFront Microbiol201892221

11 

SR Sharma R Sharma D Kar Novel Microbial Compounds as a Boon in Health Management Biotechnological Advances for Microbiology, Molecular Biology, and Nanotechnology1st Ed202277118

12 

H Moravej Z Moravej M Yazdanparast M Heiat A Mirhosseini MM Moghaddam Antimicrobial Peptides: Features, Action, and Their Resistance Mechanisms in BacteriaMicrob Drug Resist201824674767

13 

KS Makarova YI Wolf EV Koonin R Barrangou EJ Sontheimer LA Marraffini Evolutionary Classification of CRISPR-Cas SystemsCrispr: Biology and ApplicationWileyUnited States20221338

14 

GE Vanlear FW Mclafferty Biochemical aspects of high-resolution mass spectrometry. Annual review of biochemistryAnnu Rev Biochem196938289322

15 

M Kumar RK Topno MR Dikhit Bhawana GC Sahoo M Madhukar Molecular docking studies of chloroquine and its derivatives against P23pro-zbd domain of chikungunya virus: Implication in designing of novel therapeutic strategiesJ Cell Biochem20191201018298308

16 

HA Ruwandeepika GC Fernando TS Jayaweera RV Rai JA Bai An overview of biomedical, biotechnological, and industrial applications of actinomycetesNatural Products from ActinomycetesSpringerSingapore2022475508

17 

G Yu H Peng J Cao A Liao P Long J Huang Avilamycin production enhancement by mutagenesis and fermentation optimization in Streptomyces viridochromogenesWorld J Microbiol Biotechnol202238350

18 

MV Arasu GA Esmail NA Al-Dhabi Hypersaline Actinomycetes and Their Biological ApplicationsActinobacteria-Basics and Biotechnological ApplicationsIntechOpen201622945

19 

H Komaki Y Igarashi T Tamura Taxonomic positions of a nyuzenamide-producer and its closely related strainsMicroorganisms2022102349

20 

AR Gomes CL Varela AS Pires EJ Tavares-Da-Silva FM Roleira Synthetic and natural guanidine derivatives as antitumor and antimicrobial agents: A reviewBioorg Chem202313810660010.1016/j.bioorg.2023.106600

21 

AK Jha D Dhakal PT Van AR Pokhrel T Yamaguchi HJ Jung Structural modification of herboxidiene by substrate-flexible cytochrome P450 and glycosyltransferaseAppl Microbiol Biotechnol2015998342131

22 

A Spinello J Borišek M Pavlin P Janoš A Magistrato Computing metal-binding proteins for therapeutic benefitChemMedChem20211613203449

23 

DR Guay Drug forecast – the peptide deformylase inhibitors as antibacterial agentsTher Clin Risk Manag20073451325

24 

K Rochford F Chen Y Waguespack RW Figliozzi MK Kharel Q Zhang Volatile organic compound gamma-butyrolactone released upon herpes simplex virus type-1 acute infection modulated membrane potential and repressed viral infection in human neuron-like cellsPlos One2016118e161119

25 

Y Zhang W Fang K Wang Z Zhang Z Wu L Shi Napyradiomycin A4 and Its Relate Compounds, a New Anti-PRV Agent and Their Antibacterial Activities, from Streptomyces kebangsaanensis WS-68302Molecules2023282640

26 

M Kumar G Sahoo R Topno K Pandey V Ravidas M Dikhit Molecular interaction of antifungal compounds with fungal type I Polyketide synthase and preventing hepatocarcinogenesisInt J Infect Dis201873285

27 

H Bisio M Legendre C Giry N Philippe JM Alempic S Jeudy Evolution of giant pandoravirus revealed by CRISPR/Cas9Nat Commun2023141428

28 

E Franck TS Crofts History of the streptothricin antibiotics and evidence for the neglect of the streptothricin resistomenpj Antimicrob Resist20242310.1038/s44259-023-00020-5

29 

Z Zhu H Li P Yu Y Guo S Luo Z Chen SlnR is a positive pathway-specific regulator for salinomycin biosynthesis in Streptomyces albusAppl Microbiol Biotechnol2017101154757

30 

JH Lai SF Luo LJ Ho Operation of mitochondrial machinery in viral infection-induced immune responsesBiochem Pharmacol201815634856

31 

S Westhoff SB Otto A Swinkels B Bode GPV Wezel DE Rozen Spatial structure increases the benefits of antibiotic production in StreptomycesEvolution202074117987

32 

R Abdelaziz YH Tartor AB Barakat G El-Didamony MM Gado MS Zaki Alpha-sitosterol: a new antiviral agent produced by Streptomyces misakiensis and its potential activity against Newcastle disease virusBMC Vet Res202420176

33 

S M Imani L Ladouceur T Marshall R Maclachlan L Soleymani T F Didar Antimicrobial nanomaterials and coatings: Current mechanisms and future perspectives to control the spread of viruses including SARS-CoV-2ACS nano202014101234169

34 

JQ Li M Huang YN Zhang R Liu ZR Zhang QY Zhang Aglycone polyether ionophores as broad-spectrum agents inhibit multiple enveloped viruses including SARS-CoV-2 in vitro and successfully cure JEV infected micebioRxiv202010.1101/2020.10.27.354563

35 

K Summer J Browne L Liu K Benkendorff Molluscan compounds provide drug leads for the treatment and prevention of respiratory diseaseMar Drugs2020181157070

36 

N Takizawa M Yamasaki Current landscape and future prospects of antiviral drugs derived from microbial productsJ Antibiot (Tokyo)20187114552

37 

R Srinivasan A Kannappan C Shi X Lin Marine bacterial secondary metabolites: A treasure house for structurally unique and effective antimicrobial compoundsMar Drugs20211910530



jats-html.xsl


This is an Open Access (OA) journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

  • Article highlights
  • Article tables
  • Article images

Article History

Received : 12-03-2024

Accepted : 27-03-2024


View Article

PDF File   Full Text Article


Copyright permission

Get article permission for commercial use

Downlaod

PDF File   XML File   ePub File


Digital Object Identifier (DOI)

Article DOI

https://doi.org/ 10.18231/j.ijmr.2024.002


Article Metrics






Article Access statistics

Viewed: 808

PDF Downloaded: 472