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Viruses
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Novel Antiviral Targets against Emerging Viruses
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Novel Antiviral Targets against Emerging Viruses

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 13167

Special Issue Editors

Prof. Dr. Ana Carolina Gomes Jardim

E-Mail Website
Guest Editor
Laboratory of Virology, Institute of Biomedical Science, ICBIM, Federal University of Uberlândia, Uberlândia 38408-100, Brazil
Interests: viruses; arboviruses; Chikungunya virus; Zika virus; antiviral; Dengue virus; SARS-CoV-2; Mayaro virus; natural compounds; synthetic compounds
Prof. Dr. Paula Rahal

E-Mail Website
Guest Editor
Laboratory of Genomic Studies, Institute of Biosciences, Letters and Exact Sciences (IBILCE), São Paulo State University (UNESP), São Paulo 15054-000, Brazil
Interests: viruses; arboviruses; Chikungunya virus; Zika virus; antiviral; SARS-CoV-2; natural compounds; synthetic compounds

Special Issue Information

Dear Colleagues,

Diseases caused by viruses represents an important public health concern due to the possibility of outbreaks and epidemics, impacting individuals, health services, and the economy worldwide. Throughout history, outbreaks and epizootics have been described around the world from time to time, as exemplified by the current pandemic, caused by SARS-CoV-2. Therefore, the demand for antivirals against emerging viruses has increased. Additionally, tropical and subtropical countries have faced a critical scenario related to the control of arboviruses caused by Chikungunya (CHIKV), Mayaro (MAYV), Dengue (DENV), and Zika (ZIKV) viruses, which can result in long-term consequences for human health as well as high costs to health services.

Host jumps caused by direct contact with wild animals, in the case of coronaviruses and the wide distribution of vectors susceptible to viral transmission of arboviruses raise concerns about the possible emergence of future epidemics involving emerging viruses. In addition, RNA viruses have high frequencies of mutation during replication, which is related to the virus’ ability to evade the immune response and challenges the effectiveness of antivirals. Therefore, it is essential to develop a variety of antiviral molecules that can abrogate viral infection and that could also be used in combined therapies.

Prof. Dr. Ana Carolina Gomes Jardim
Prof. Dr. Paula Rahal
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antiviral
  • arboviruses
  • Chikungunya virus
  • Zika virus
  • Mayaro virus
  • SARS-CoV-2
  • natural and synthetic compounds

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Published Papers (6 papers)

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Research

16 pages, 4857 KiB  
Article
Naturally Derived Terpenoids Targeting the 3Dpol of Foot-and-Mouth Disease Virus: An Integrated In Silico and In Vitro Investigation
by Natjira Mana, Sirin Theerawatanasirikul, Ploypailin Semkum and Porntippa Lekcharoensuk
Viruses 2024, 16(7), 1128; https://doi.org/10.3390/v16071128 - 14 Jul 2024
Viewed by 1233
Abstract
Foot-and-mouth disease virus (FMDV) belongs to the Picornaviridae family and is an important pathogen affecting cloven-hoof livestock. However, neither effective vaccines covering all serotypes nor specific antivirals against FMDV infections are currently available. In this study, we employed virtual screening to screen for [...] Read more.
Foot-and-mouth disease virus (FMDV) belongs to the Picornaviridae family and is an important pathogen affecting cloven-hoof livestock. However, neither effective vaccines covering all serotypes nor specific antivirals against FMDV infections are currently available. In this study, we employed virtual screening to screen for secondary metabolite terpenoids targeting the RNA-dependent RNA polymerase (RdRp), or 3Dpol, of FMDV. Subsequently, we identified the potential antiviral activity of the 32 top-ranked terpenoids, revealing that continentalic acid, dehydroabietic acid (abietic diterpenoids), brusatol, bruceine D, and bruceine E (tetracyclic triterpenoids) significantly reduced cytopathic effects and viral infection in the terpenoid-treated, FMDV-infected BHK-21 cells in a dose-dependent manner, with nanomolar to low micromolar levels. The FMDV minigenome assay demonstrated that brusatol and bruceine D, in particular, effectively blocked FMDV 3Dpol activity, exhibiting IC50 values in the range of 0.37–0.39 µM and surpassing the efficacy of the antiviral drug control, ribavirin. Continentalic acid and bruceine E exhibited moderate inhibition of FMDV 3Dpol. The predicted protein–ligand interaction confirmed that these potential terpenoids interacted with the main catalytic and bystander residues of FMDV 3Dpol. Additionally, brusatol and bruceine D exhibited additive effects when combined with ribavirin. In conclusion, terpenoids from natural resources show promise for the development of anti-FMD agents. Full article
(This article belongs to the Special Issue Novel Antiviral Targets against Emerging Viruses)
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18 pages, 4227 KiB  
Article
Small Molecules Targeting 3C Protease Inhibit FMDV Replication and Exhibit Virucidal Effect in Cell-Based Assays
by Sirin Theerawatanasirikul, Varanya Lueangaramkul, Achiraya Pantanam, Natjira Mana, Ploypailin Semkum and Porntippa Lekcharoensuk
Viruses 2023, 15(9), 1887; https://doi.org/10.3390/v15091887 - 6 Sep 2023
Cited by 3 | Viewed by 1600
Abstract
Foot-and-mouth disease (FMD) is a highly contagious disease in cloven-hoofed animals, caused by the foot-and-mouth disease virus (FMDV). It is endemic in Asia and Africa but spreads sporadically throughout the world, resulting in significant losses in the livestock industry. Effective anti-FMDV therapeutics could [...] Read more.
Foot-and-mouth disease (FMD) is a highly contagious disease in cloven-hoofed animals, caused by the foot-and-mouth disease virus (FMDV). It is endemic in Asia and Africa but spreads sporadically throughout the world, resulting in significant losses in the livestock industry. Effective anti-FMDV therapeutics could be a supportive control strategy. Herein, we utilized computer-aided, structure-based virtual screening to filter lead compounds from the National Cancer Institute (NCI) diversity and mechanical libraries using FMDV 3C protease (3Cpro) as the target. Seven hit compounds were further examined via cell-based antiviral and intracellular protease assays, in which two compounds (NSC116640 and NSC332670) strongly inhibited FMDV, with EC50 values at the micromolar level of 2.88 µM (SI = 73.15) and 5.92 µM (SI = 11.11), respectively. These compounds could inactivate extracellular virus directly in a virucidal assay by reducing 1.00 to 2.27 log TCID50 of the viral titers in 0–60 min. In addition, the time-of-addition assay revealed that NSC116640 inhibited FMDV at the early stage of infection (0–8 h), while NSC332670 diminished virus titers when added simultaneously at infection (0 h). Both compounds showed good FMDV 3Cpro inhibition with IC50 values of 10.85 µM (NSC116640) and 4.21 µM (NSC332670). The molecular docking of the compounds on FMDV 3Cpro showed their specific interactions with amino acids in the catalytic triad of FMDV 3Cpro. Both preferentially reacted with enzymes and proteases in physicochemical and ADME analysis studies. The results revealed two novel small molecules with antiviral activities against FMDV and probably related picornaviruses. Full article
(This article belongs to the Special Issue Novel Antiviral Targets against Emerging Viruses)
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26 pages, 5718 KiB  
Article
Mannose-Binding Lectins as Potent Antivirals against SARS-CoV-2
by Victória Riquena Grosche, Leandro Peixoto Ferreira Souza, Giulia Magalhães Ferreira, Marco Guevara-Vega, Tamara Carvalho, Romério Rodrigues dos Santos Silva, Karla Lilian Rodrigues Batista, Rodrigo Paolo Flores Abuna, João Santana Silva, Marília de Freitas Calmon, Paula Rahal, Luis Cláudio Nascimento da Silva, Bruno Silva Andrade, Claudener Souza Teixeira, Robinson Sabino-Silva and Ana Carolina Gomes Jardim
Viruses 2023, 15(9), 1886; https://doi.org/10.3390/v15091886 - 6 Sep 2023
Cited by 3 | Viewed by 2148
Abstract
The SARS-CoV-2 entry into host cells is mainly mediated by the interactions between the viral spike protein (S) and the ACE-2 cell receptor, which are highly glycosylated. Therefore, carbohydrate binding agents may represent potential candidates to abrogate virus infection. Here, we evaluated the [...] Read more.
The SARS-CoV-2 entry into host cells is mainly mediated by the interactions between the viral spike protein (S) and the ACE-2 cell receptor, which are highly glycosylated. Therefore, carbohydrate binding agents may represent potential candidates to abrogate virus infection. Here, we evaluated the in vitro anti-SARS-CoV-2 activity of two mannose-binding lectins isolated from the Brazilian plants Canavalia brasiliensis and Dioclea violacea (ConBR and DVL). These lectins inhibited SARS-CoV-2 Wuhan-Hu-1 strain and variants Gamma and Omicron infections, with selectivity indexes (SI) of 7, 1.7, and 6.5, respectively for ConBR; and 25, 16.8, and 22.3, for DVL. ConBR and DVL inhibited over 95% of the early stages of the viral infection, with strong virucidal effect, and also protected cells from infection and presented post-entry inhibition. The presence of mannose resulted in the complete lack of anti-SARS-CoV-2 activity by ConBR and DVL, recovering virus titers. ATR-FTIR, molecular docking, and dynamic simulation between SARS-CoV-2 S and either lectins indicated molecular interactions with predicted binding energies of −85.4 and −72.0 Kcal/Mol, respectively. Our findings show that ConBR and DVL lectins possess strong activities against SARS-CoV-2, potentially by interacting with glycans and blocking virus entry into cells, representing potential candidates for the development of novel antiviral drugs. Full article
(This article belongs to the Special Issue Novel Antiviral Targets against Emerging Viruses)
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15 pages, 3449 KiB  
Article
Antiviral Activities of Streptomyces KSF 103 Methanolic Extracts against Dengue Virus Type-2
by Nurfatihah Zulkifli, Jasmine-Elanie Khairat, Adzzie-Shazleen Azman, Nur-Faralyza Mohd Baharudin, Nurul-Adila Malek, Syafiq-Asnawi Zainal Abidin, Sazaly AbuBakar and Pouya Hassandarvish
Viruses 2023, 15(8), 1773; https://doi.org/10.3390/v15081773 - 20 Aug 2023
Viewed by 1741
Abstract
Dengue has long been a serious health burden to the global community, especially for those living in the tropics. Despite the availability of vaccines, effective treatment for the infection is still needed and currently remains absent. In the present study, the antiviral properties [...] Read more.
Dengue has long been a serious health burden to the global community, especially for those living in the tropics. Despite the availability of vaccines, effective treatment for the infection is still needed and currently remains absent. In the present study, the antiviral properties of the Streptomyces sp. KSF 103 methanolic extract (Streptomyces KSF 103 ME), which consists of a number of potential antiviral compounds, were investigated against dengue virus serotype 2 (DENV-2). The effects of this extract against DENV-2 replication were determined using the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Findings from the study suggested that the Streptomyces KSF 103 ME showed maximum inhibitory properties toward the virus during the virus entry stage at concentrations of more than 12.5 µg/mL. Minimal antiviral activities were observed at other virus replication stages; adsorption (42% reduction at 50 µg/mL), post-adsorption (67.6% reduction at 50 µg/mL), prophylactic treatment (68.4% and 87.7% reductions at 50 µg/mL and 25 µg/mL, respectively), and direct virucidal assay (48% and 56.8% reductions at 50 µg/mL and 25 µg/mL, respectively). The Streptomyces KSF 103 ME inhibited dengue virus replication with a 50% inhibitory concentration (IC50) value of 20.3 µg/mL and an International System of Units (SI) value of 38.9. The Streptomyces KSF 103 ME showed potent antiviral properties against dengue virus (DENV) during the entry stage. Further studies will be needed to deduce the antiviral mechanisms of the Streptomyces KSF 103 ME against DENV. Full article
(This article belongs to the Special Issue Novel Antiviral Targets against Emerging Viruses)
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14 pages, 1482 KiB  
Article
Antiviral Activity of Catechin against Dengue Virus Infection
by Bowen Yi, Benjamin Xuan Zheng Chew, Huixin Chen, Regina Ching Hua Lee, Yuhui Deborah Fong, Wei Xin Chin, Chee Keng Mok and Justin Jang Hann Chu
Viruses 2023, 15(6), 1377; https://doi.org/10.3390/v15061377 - 15 Jun 2023
Cited by 5 | Viewed by 3220
Abstract
Dengue virus (DENV) is the cause of dengue fever, infecting 390 million people worldwide per year. It is transmitted to humans through the bites of mosquitoes and could potentially develop severe symptoms. In spite of the rising social and economic impact inflicted by [...] Read more.
Dengue virus (DENV) is the cause of dengue fever, infecting 390 million people worldwide per year. It is transmitted to humans through the bites of mosquitoes and could potentially develop severe symptoms. In spite of the rising social and economic impact inflicted by the disease on the global population, a conspicuous lack of efficacious therapeutics against DENV still persists. In this study, catechin, a natural polyphenol compound, was evaluated as a DENV infection inhibitor in vitro. Through time-course studies, catechin was shown to inhibit a post-entry stage of the DENV replication cycle. Further investigation revealed its role in affecting viral protein translation. Catechin inhibited the replication of all four DENV serotypes and chikungunya virus (CHIKV). Together, these results demonstrate the ability of catechin to inhibit DENV replication, hinting at its potential to be used as a starting scaffold for further development of antivirals against DENV infection. Full article
(This article belongs to the Special Issue Novel Antiviral Targets against Emerging Viruses)
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17 pages, 1745 KiB  
Article
The Dimeric Peptide (KKYRYHLKPF)2K Shows Broad-Spectrum Antiviral Activity by Inhibiting Different Steps of Chikungunya and Zika Virus Infection
by Gabriela Miranda Ayusso, Maria Letícia Duarte Lima, Paulo Ricardo da Silva Sanches, Igor Andrade Santos, Daniel Oliveira Silva Martins, Pâmela Jóyce Previdelli da Conceição, Tamara Carvalho, Vivaldo Gomes da Costa, Cíntia Bittar, Andres Merits, Norival Alves Santos-Filho, Eduardo Maffud Cilli, Ana Carolina Gomes Jardim, Marilia de Freitas Calmon and Paula Rahal
Viruses 2023, 15(5), 1168; https://doi.org/10.3390/v15051168 - 14 May 2023
Cited by 3 | Viewed by 2409
Abstract
Chikungunya virus (CHIKV) and Zika virus (ZIKV) are important disease-causing agents worldwide. Currently, there are no antiviral drugs or vaccines approved to treat these viruses. However, peptides have shown great potential for new drug development. A recent study described (p-BthTX-I)2K [(KKYRYHLKPF) [...] Read more.
Chikungunya virus (CHIKV) and Zika virus (ZIKV) are important disease-causing agents worldwide. Currently, there are no antiviral drugs or vaccines approved to treat these viruses. However, peptides have shown great potential for new drug development. A recent study described (p-BthTX-I)2K [(KKYRYHLKPF)2K], a peptide derived from the Bothropstoxin-I toxin in the venom of the Bothrops jararacussu snake, showed antiviral activity against SARS-CoV-2. In this study, we assessed the activity of this peptide against CHIKV and ZIKV and its antiviral action in the different stages of the viral replication cycle in vitro. We observed that (p-BthTX-I)2K impaired CHIKV infection by interfering with the early steps of the viral replication cycle, reducing CHIKV entry into BHK-21 cells specifically by reducing both the attachment and internalization steps. (p-BthTX-I)2K also inhibited the ZIKV replicative cycle in Vero cells. The peptide protected the cells against ZIKV infection and decreased the levels of the viral RNA and the NS3 protein of this virus at viral post-entry steps. In conclusion, this study highlights the potential of the (p-BthTX-I)2K peptide to be a novel broad-spectrum antiviral candidate that targets different steps of the replication cycle of both CHIKV and ZIKV. Full article
(This article belongs to the Special Issue Novel Antiviral Targets against Emerging Viruses)
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