COVID-19와 같은 전염병 감염 시나리오 전반에 걸쳐 펩타이드 기반 치료법을 발견하고 설계하는 개발 시대의 추세는 보다 효율적이고 저렴한 치료 환경으로 발전할 수 있습니다. 결과적으로, 그들의 단백질 분해 약화는 천연 펩타이드 약물의 단점 중 하나입니다. 펩티도미메틱스는 이 단점을 해결하는 데 도움이 될 수 있습니다. 이 리뷰에서 펩타이드 및 펩타이드 기반 약물 발견은 숙주 안지 오텐신 전환 효소-2(ACE2) 수용체 및 바이러스 스파이크 (S)단백질의 연관성을 포함하는 중증 코로나바이러스 폐색전 증후군(SARS-CoV-2)의 주요 진입 기전 중 하나를 표적으로 요약했습니다. 또한, 펩타이드 기반의 새로운 치료법을 통해 COVID-19에 대해 연구된 단백질, 펩타이드 및 기타 가능한 조치의 이점을 다룹니다. 그리고 펩타이드 기반 약물 치료 환경의 개요는 진화적 관점, 구조적 특성, 작동 한계값 및 치료 영역에 대한 설명으로 구성된다

Melia azedarach is commonly used in traditional and folk medicine in Korea and China to treat a variety of diseases including diarrheal, diabetic, rheumatic, and hypertensive disease. The aim of this study was to determine the potential prophylactic and therapeutic effects of Melia azedarach against a broad spectrum of viruses in in vitro cell culture model and the protective effect against different influenza A subtypes in BALB/c mice model. An effective dose of pre-treatment, co-treatment, and post-treatment of Melia azedarach significantly reduced the replication of coxsackievirus, herpes simplex virus, influenza A virus, enterovirus, and bovine rhinovirus in both epithelial and macrophage cell lines. Melia azedarach treatment remarkably promoted the phosphorylation of the key molecules associated with the type-1 interferon and NF-κB signaling pathways. Furthermore, it induced the secretion of type-1 interferon and pro-inflammatory cytokines and the subsequent stimulation of the antiviral state in both epithelial and macrophage cells. Interestingly, oral inoculation of an effective dose of herb extract significantly improved viral clearance in the lungs of BALB/c mice, thus exhibiting protection against several subtypes of influenza A virus. Together with our results indicate that an extracts of Melia azedarach and its components could exhibit a potential natural source of an antiviral drug candidate for a broad spectrum of viruses in animal and humans.

Cordyceps species are known to produce numerous active components and are used for diverse medicinal purposes because of their varied physiological activities, including their anticancer, anti-inflammatory, and antimicrobial effects. Cordycepin, one of adenosine analogues, differs from adenosine in that its ribose lacks an oxygen atom at the 3' position. Cordycepin has been reported to be a main effector molecule in Cordyceps extracts that executes antiviral activities against several viruses including influenza virus, plant viruses, human immunodeficiency virus (HIV), murine leukemia virus, and Epstein-Barr virus (EBV). In addition, adenosine and its deaminase inhibitor showed strong antiviral potentials that were about 4,000 times more potent than the activity of the direct inhibitory effect by adenine arabinoside on Herpes simplex virus (HSV)-1, suggesting adenosine itself plays an important role to produce antiviral activities. In this study, we show that cordycepin and adenosine possess antiviral and antitumor activities against EBV and EBVassociated gastric carcinoma, respectively. Furthermore, we report epigenetic mechanisms used by cordycepin and adenosine to exert their antiviral and antitumor effects.

An oxidative fumigant is potent to kill insect pests infesting stored grains. Its oxidative activity generates reactive oxygen species (ROS), which has been considered to be a main insecticidal factor. Furthermore, the oxidative fumigant has cytotoxic effect to insect cell lines, but the cytotoxicity is abrogated by antioxidant treatment. This study aimed to extend the usefulness of the oxidative fumigant in terms of medical purpose against cancer cells. Five cancer cell lines HCT 116 (human colorectal), Lovo (human colorectal), SW480 (human colorectal), MDA-MB-231 (human breast), and MCF-7 (human breast) were tested to determine their susceptibility to the oxidative fumigant with reference to two insect cell lines (Sf9 and Hi-Five). All cancer cell lines were highly susceptible to the oxidative fumigant, compared to the insect cell lines. Interestingly, basal ROS levels of the cancer cell lines were much higher than the insect cell lines. Furthermore, the oxidative fumigant significantly increased the ROS levels in the cancer cells. Treatment of vitamin E as an antioxidant mitigated the cytotoxicity of the oxidative fumigant. Thus, the high susceptibility of cancer cells to the oxidative fumigant may be induced by their high inducible ROS production. This study also investigated the antiviral activity of the oxidative fumigant against insect and plant viruses. The oxidative fumigant significantly inactivated a baculovirus (dsDNA virus) by inhibiting polyhedral production in Sf9 cells. It also inactivated tobacco mosaic virus (ssRNA virus) by suppressing phytopathogenicity. These results support a broad effect of the oxidative fumigant, which can be applied to agricultural and medical purposes.

In this study, the veridical efficacy of an aquatic disinfectant tablet composed to calcium hypochlorite against red sea bream iridovirus (RBIV). A veridical efficacy was determined with the viability of RBIV contacted with the disinfectant in viral stock cultured in fat head minnow cell line. An aquatic disinfectant tablet and RBIV were reacted on the distilled water (DW), hard water (HW) or organic matter suspension (OM) condition. On DW and HW condition, RBIV was inactivated with 25,000 fold dilutions of an aquatic disinfectant tablet. With the investigation of the antiviral effect of the disinfectant on OM condition, RBIV was inactivated on 22,000 fold dilutions of an aquatic disinfectant tablet. As an aquatic disinfectant tablet possesses veridical efficacy against RBIV, the disinfectant solution can be used to limit the spread of cultured marine fish viral disease.

Highly pathogenic avian influenza virus (HPAIV) is already panzootic in poultry and caused a considerable economic loss in poultry industry. In addition, HPAIV continues to cross species barriers to infect humans and other mammals, often with fatal outcomes. In this study, the virucidal efficacy of Citra-Kill® composed to quaternary ammonium chloride and citric acid was investigated against avian influenza H9N2 virus (AIV). A virucidal efficacy was determined with the viability of AIV contacted with the disinfectant in the allantoic membrane of chicken embryos. Citra-Kill® and AIV was reacted on the distilled water (DW), hard water (HW) or organic matter suspension (OM) condition. On DW condition, AIV was inactivated with 2,000 fold dilutions of Citra-Kill®. When the antiviral effect on HW condition was evaluated, the antiviral activity of the disinfectant showed on 1,500 fold dilutions against AIV. With the investigation of the antiviral effect of the disinfectant on OM condition, AIV was inactivated on 500 fold dilutions of Citra-Kill®. As Citra-Kill® possesses virucidal efficacy against AIV, the disinfectant solution can be used to limit the spread of animal viral diseases.

Mosquito-borne viral pathogens infect millions of people worldwide, often resulting in fatal infections. Our research interests in mosquito vector biology focuses on understanding of the molecular and genetic basis of mosquito resistance to arbovirus infections. Unlike mammalian cells including humans, for instance, mosquito cells do not show pathologic symptoms when infected by arboviruses. This observation led us to embarking a microarray study to investigate mosquito-virus interactions using Anopheles gambiae and o’nyong-nyong virus (ONNV) as a model system. As a result, we found that transcription of the hsc70B gene is increased about 2.6-fold in ONNV-infected An. gambiae compared to non-infected controls. Subsequently, in vivo RNAi silencing of the hsc70B transcript caused enhanced ONNV replication in female mosquitoes. Therefore, these results suggest that the hsc70B protein has an inhibitory effect on ONNV replication. A promoter analysis of the hsc70B locus further demonstrated that the hsc70B promoter is able to induce transcription of hsc70B in response to ONNV infection. In addition, hsc70B transcription was also induced by West Nile or La Crosse virus infection. Collectively, our findings indicate that hsc70B plays a role in suppressing virus replication as a general antiviral mechanism. Implications of hsc70B research and our other research endeavors toward the control of mosquito-borne infectious diseases will be discussed.

An endoparasitoid wasp, Cotesia plutellae, parasitizes larvae of the diamondback moth, Plutella xylostella, with its symbiotic polydnavirus, C. plutellae bracovirus (CpBV). This study analyzed the role of Inhibitor-kB (IkB)-like genes encoded in CpBV in suppressing host antiviral and antimicrobial responses. Identified eight CpBV-IkBs are scattered on different viral genome segments and showed high homologies with other bracoviral IkBs in their amino acid sequences. Compared to an insect ortholog (e.g., Cactus of Drosophila melanogaster), they possessed a shorter ankyrin repeat domain without any regulatory domains. The eight CpBV-IkBs are, however, different in their promoter components and expression patterns in the parasitized host. To test their inhibitory activity on host antiviral response, a midgut response of P. xylostella against baculovirus infection was used as a model reaction. When the larvae were orally fed the virus, they exhibited melanotic responses of midgut epithelium, which increased with baculovirus dose and incubation time. Parasitized larvae exhibited a significant reduction in the midgut melanotic response, compared to nonparasitized larvae. Micro-injection of each of the four CpBV genome segments containing CpBV-IkBs into the hemocoel of nonparasitized larvae showed the gene expressions of the encoded IkBs and suppressed the midgut melanotic response in response to the baculovirus treatment. When nonparasitized larvae were orally administered with a recombinant baculovirus containing CpBV-IkB, they showed a significant reduction in midgut melanotic response and an enhanced susceptibility to the baculovirus infectivity. The transiently expressed CpBV-IkB3 inhibited expression of hemolin, but did not those of lysozyme and cecropin in P. xylostella, while both lysozyme and cecropin were inhibited in the treated Spodoptera exigua. When the recombinant AcNPV was mixed with Bacillus thuringiensis subsp. kurstaki (Bt), the bacterial pathogenicity was significantly enhanced in a dose-dependent manner, compared to a Bt mixture with an AcMNPV recombined with an enhanced green fluorescence protein gene.

The diamondback moth, Plutella xylostella, is reluctant to a baculovirus, Autographa california nucleopolyhedrosis virus (AcNPV) at its oral administration. However, parasitization by an endoparasitoid wasp, Cotesia plutellae, enhances the viral susceptibility. This study analyzed an antiviral activity of P. xylostella in response to the viral infection and determined the parasitic factor inhibiting the antiviral mechanism. For the analysis of antiviral activity of P. xylostella, a recombinant AcNPV expressing enhanced green fluorescence (AcNPV-EGFP) was orally adminstered to lavae of P. xylostella. After 24 h, EGFP expression was observed in the midgut tissue at a confocal-FITC mode. At the same time, a characteristic midgut melanotic response (MMR) was observed in some midgut regions under a phase contrast microscope. Thereafter, the EGFP signal was attenuated, while MMR spread on most midgut region. When the MMR was scored from 0 to 5 by the intensity of melanized cell density, it increased in time- and dose-dependent manners at the viral administration per os. These results suggest that the MMR is an antiviral activity of P. xylostella. This antiviral activity was significantly attenuated by C. plutellae parasitism. The parasitized P. xylostella showed significant decrease in the MMR score compared to nonparasitized larvae when they were orally administered with the same dose of AcNPV. To determine the parasitic factor(s) inhibiting the antiviral activity from the symbiotic polydnavirus of C. plutellae (C. plutellae bracovirus: CpBV), CpBV-IkB, which is a viral homolog of NFkB inhibitor and has been considered as an antiviral factor as in other polydnaviruses, was tested. A recombinant AcNPV expressing CpBV-IkB (AcNPV-IkB) was constructed and administered to P. xylostella larvae. As expected, AcNPV-IkB significantly decreased the antiviral activity measured by the MMR score compared to AcNPV-EGFP treatment. This study suggests that CpBV-IkB plays an antiviral parasitic role in the molecular interactions between P. xylostella and C. plutellae.

식중독 원인균 S. aureus, E. coli O157:H7, S. typhimurium, S. enteritidis, L. monocytogenes, 장티프스 원인균 S. typhi, 패혈증 원인균 V. parahaemolyticus, 세균성 이질 원인균 S. sonnei를 20℃에서 30분간 그린존^TM과 접촉시킨 결과 최소 3배 희석액부터 최대 24배 희석액에서 균에 대한 살멸 효과를 나타내었다. 그린존^TM 3배 희석액을 이용하여 30초, 1부, 5분간 균과 접촉시킨 결과 S. aureus만 제외하고 모두 30초에 100% 살멸하는 효과를 나타내었다. 그린존^TM을 이용하여 사스의 원인체와 동일한 바이러스인 코로나 바이러스에 대한 살바이러스 효과를 본 결과 제품의 5배 희석액까지 유효한 살바이러스 효과를 보였다. 사람과 접촉이 많은 애완견 바이러스인 파보바이러스(CPV), 디스템퍼바이러스(CDV)에 대하여 시험한 결과 유기물과 경수 등의 악조건에서도 바이러스를 살멸하는 효과를 나타내었다. 그린존^TM을 이용한 회와 냉장육 등에서의 적용 시험결과 미생물 생육이 현저히 저해됨을 알 수 있었다. 체소내의 미생물에 대한 살멸효과 시험에서도 미생물의 수가 현저하게 감소하였고, 특히 대장균의 수가 현저하게 감소하였다. 그린존^TM은 세균, 바이러스의 살멸에 탁월한 효과를 보이며, 음식물에 직접 처리할 시에도 그 안전성과 효능이 입증되었다.

Newcastle disease virus(NDV) 감염된 baby hamster kidney(BHK) 세포에서 syncytium(합포체) 형성은 세포막 표면으로의 수송된 바이러스 당단백질 hemagglutinin-neuramidase(HN)에 의해 일어난다. HAU 값은 추출물의 농도가 25과 3.2 ug/mL 사이에서는 현저하게 감소하였으나, NDV 감염된 HAD(%)는 25 ug/mL 농도에서 광범위한 흡착능의 감소를 나타내 바이러스 당단백질의 세포내 생합성은 저해되지 않았다. 그러므로, 약용식물인 마황 메탄올 추출물이 바이러스 당단백질의 세포막으로의 수송과 함께 합포체 형성을 저해하여 항바이러스 작용을 하였다. 또한 마황 추출물의 저해활성을 조사한 결과 α-glucosidase에 대한 추출물의 IC50은 18μg/mL이었으며, β-glucosidase, α-mannosidase, β-mannosidase에 대한 마황 추출물의 IC50은 각각 60, 40, 150μg/mL로 나타나 β-type glycosidases 보다 α-type glycosidase에 대한 효소활성 저해능이 우수하였다. 따라서 IC50농도에서는 세포내에서 당단백질 생합성은 저해되지 않으며 당단백질의 수송을 저해하는 것으로 판단되었으며 향후 항바이러스 관련 작용기작의 연구가 필요하다고 판단된다.