Publications by authors named "Shan Cen"

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the pathogen of coronavirus disease (COVID-19) causing a pandemic with growing global transmission. The viral RNA-dependent RNA polymerase (RdRp) is conserved especially for variants of concern (VOCs), making it as an effective antivirals target. Due to the proofreading activity of coronavirus nsp14/nsp10, limited the efficacy of nucleoside analogs in vivo.

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Influenza A virus (IAV) poses a serious global threat to public health. There is an urgent need to develop new anti-IAV agents due to the limitations of the current antiviral drugs in clinical practice. Herein, based on compound I-13e, we designed and synthesized 23 substituted quinoline derivatives containing piperazine moieties and evaluated their in vitro anti-IAV activity.

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Unlabelled: Enterovirus-A71 (EV-A71) is the second most common causative agent after coxsackievirus A16 of hand, foot, and mouth disease. The capsids of EV-A71 consist of 60 copies of each of the four viral structural proteins (VP1-VP4). VP1 is highly exposed and surface accessible, playing a central role in virus particle assembly, attachment, and entry.

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The safety and efficacy of the lipid nanoparticle (LNP) delivery system are crucial for the successful development of messenger RNA vaccines. We designed and synthesized a series of ketal ester lipids (KELs), featuring a biodegradable ketal moiety in the linker and ester segments in the tail. Through iterative optimization of the head and tail groups of KELs, we tuned the pKa and molecular shapes, and identified (4S)-KEL12 as a safe and efficient ionizable lipid for mRNA delivery.

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The interaction of PD-L1 and PD-1 transmits the inhibitory signal to reduce the proliferation of antigen-specific T-cells in lymph nodes. The expression of PD-L1 confers a potential escaping mechanism of tumors from the host immune system. Blocking the interaction of PD-1 and PD-L1 enables tumor-reactive T cells to overcome regulatory mechanisms and induce an effective antitumor response.

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Tuberculosis (TB) is a high mortality infectious disease caused by Mycobacterium tuberculosis (Mtb), and often develops into latent infection. About 5~10% of latent infections turn into active tuberculosis when the host immune system becomes deficient. Therefore, exploring the latent infection mechanism of Mtb is pivotal for the prevention and treatment of tuberculosis.

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Article Synopsis
  • - Tuberculosis (TB) is a significant global health issue, necessitating research for new anti-TB drugs to aid in elimination efforts.
  • - A new class of anti-TB agents was identified, with two compounds showing excellent activity against TB bacteria and low toxicity.
  • - These compounds also demonstrated good metabolic stability and oral bioavailability, exhibiting protective effects in zebrafish studies, making them strong candidates for further research.
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The global prevalence of RNA virus infections has presented significant challenges to public health in recent years, necessitating the expansion of its alternative therapeutic library. Due to its evolutional conservation, RNA-dependent RNA polymerase (RdRp) has emerged as a potential target for broad-spectrum antiviral nucleoside analogues. However, after over half a century of structural modification, exploring unclaimed chemical space using frequently-used structural substitution methods to design new nucleoside analogues is challenging.

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Type I interferon (IFN) inhibits a wide spectrum of viruses through stimulating the expression of antiviral proteins. As an IFN-induced protein, myxovirus resistance B (MXB) protein was reported to inhibit multiple highly pathogenic human viruses. It remains to be determined whether MXB employs a common mechanism to restrict different viruses.

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Influenza A viruses have a wide range of hosts and are highly infectious, which can cause zoonotic diseases and pose a serious public health threat to human safety. An influenza pandemic could outbreak if new strains gain the ability of human-to-human transmission, either by genetic mutation or by gene reassortment. It is an urgent issue for the scientific community to reveal the genetic basis and molecular mechanisms underlying the interspecies transmission of influenza viruses, which will provide important implications for the effective monitoring and prevention of potential influenza pandemics.

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Article Synopsis
  • HPV 16 and 18 are linked to various cancers, and although preventative vaccines exist, there is a pressing need for therapeutic vaccines to treat existing HPV infections.
  • The study introduces a new mRNA-based therapeutic vaccine, mHTV-03E2, formulated in lipid nanoparticles, which effectively triggers strong immune responses in mice, resulting in reduced tumor growth and improved survival rates.
  • Moreover, mHTV-03E2 shows promise when used in combination with immune checkpoint inhibitors, enhancing its effectiveness in fighting cancers associated with HPV16 and HPV18 infections.
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Human norovirus (HuNoV), a primary cause of non-bacterial gastroenteritis, currently lacks approved treatment. RdRp is vital for virus replication, making it an attractive target for therapeutic intervention. By application of structure-based virtual screening procedure, we present CX-6258 hydrochloride hydrate as a potent RdRp non-nucleoside inhibitor, effectively inhibiting HuNoV RdRp activity with an IC of 3.

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Long interspersed elements-1(LINE-1) is the only autonomous transposon in human genome,and its retrotransposition results in change of cellular genome structure and function, leading occurrence of various severe diseases. As a central key intermediated component during life cycle of LINE-1 retrotransposition, the host modification of LINE-1 mRNA affects the LINE-1 transposition directly. N-adenosine methylation(mA), the most abundant epigenetic modification on eukaryotic RNA, is dynamically reversible.

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Human papillomavirus (HPV) infections account for several human cancers. There is an urgent need to develop therapeutic vaccines for targeting preexisting high-risk HPV (such as HPV 16 and 18) infections and lesions, which are insensitive to preventative vaccines. In this study, we developed a lipid nanoparticle-formulated mRNA-based HPV therapeutic vaccine (mHTV), mHTV-02, targeting the E6/E7 of HPV16 and HPV-18.

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Zika virus (ZIKV) disease has been given attention due to the risk of congenital microcephaly and neurodevelopmental disorders after ZIKV infection in pregnancy, but no vaccine or antiviral drug is available. Based on a previously reported ZIKV inhibitor ZK22, a series of novel 1-aryl-4-arylmethylpiperazine derivatives was designed, synthesized, and investigated for antiviral activity by quantify cellular ZIKV RNA amount using RT-qPCR method in ZIKV-infected human venous endothelial cells (HUVECs) assay. Structure-activity relationship (SAR) analysis demonstrated that anti-ZIKV activity of 1-aryl-4-arylmethylpiperazine derivatives is not correlated with molecular hydrophobicity, multiple new derivatives with pyridine group to replace the benzonitrile moiety of ZK22 showed stronger antiviral activity, higher ligand lipophilicity efficiency as well as lower cytotoxicity.

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A new linear thiopeptide, bernitrilecin (1), was isolated from sp. CPCC 203702. Compound 1 is the first example of a nitrile-bearing thiopeptide.

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Type VI secretion systems (T6SSs) deliver effectors into target cells. Besides structural and effector proteins, many other proteins, such as adaptors, co-effectors and accessory proteins, are involved in this process. MIX domains can assist in the delivery of T6SS effectors when encoded as a stand-alone gene or fused at the N-terminal of the effector.

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Zika virus (ZIKV) belongs to Flaviviridae, the Flavivirus genus. Its infection causes congenital brain abnormalities and Guillain-Barré syndrome. However, there are no effective vaccines, no FDA-approved drugs to manage ZIKV infection.

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Long interspersed element 1 (LINE-1) is the only currently known active autonomous transposon in humans, and its retrotransposition may cause deleterious effects on the structure and function of host cell genomes and result in sporadic genetic diseases. Host cells therefore developed defense strategies to restrict LINE-1 mobilization. In this study, we demonstrated that IFN-inducible Schlafen5 (SLFN5) inhibits LINE-1 retrotransposition.

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Long interspersed element 1 (LINE-1) is the only active autonomous mobile element in the human genome. Its transposition can exert deleterious effects on the structure and function of the host genome and cause sporadic genetic diseases. Tight control of LINE-1 mobilization by the host is crucial for genetic stability.

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There are six new phthalide derivatives Verbalide A ~ F (1-6) together with another known derivative (7) isolated from the endophytic fungus Preussia sp. CPCC 400972. Their structures were established by comprehensive spectroscopic analyses, including NMR and HRESIMS.

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Vaccines and drugs are two effective medical interventions to mitigate SARS-CoV-2 infection. Three SARS-CoV-2 inhibitors, remdesivir, paxlovid, and molnupiravir, have been approved for treating COVID-19 patients, but more are needed, because each drug has its limitation of usage and SARS-CoV-2 constantly develops drug resistance mutations. In addition, SARS-CoV-2 drugs have the potential to be repurposed to inhibit new human coronaviruses, thus help to prepare for future coronavirus outbreaks.

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Triterpenoids are a large and medicinally important group of natural products with a wide range of biological and pharmacological effects. Among them, malabaricane-type triterpenoids are a rare group of terpenoids with a 6,6,5-tricyclic ring system, and a few malabaricane triterpene synthases have been characterized to date. Here, an arabidiol synthase AmAS for the formation of the malabaricane-type 6,6,5-tricyclic triterpenoid skeleton in astramalabaricosides biosynthesis was characterized from .

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LC-MS/MS-based molecular networking annotation coupled H NMR detection allowed the depiction of the soft coral to produce a profile of dolabellane-type diterpenoids. Chromatographic separation of the EtOAc fraction resulted in the isolation of 12 undescribed dolabellane-type diterpenoids, namely, clavirolides J-U (-) Their structures were characterized by the extensive analysis of the spectroscopic data, including the calculated ECD and X-ray diffraction for the configurational assignments. Clavirolides J-K are characterized by a 1,11- and 5,9-fused tricyclic tetradecane scaffold fused with a α,β-unsaturated-δ-lactone, and clavirolide L possesses a 1,11- and 3,5-fused tricyclic tetradecane scaffold, which extend the dolabellane-type scaffolds.

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