Mutagenesis studies suggest a mechanism for influenza polymerase stalling during polyadenylation.

Influenza polymerase (FluPol) carries out both viral transcription and replication using the same viral genome segment as a template to yield distinct end products. However, it remains largely unclear how FluPol synthesizes transcripts containing poly (A) tails during transcription termination, while producing fully complementary products during replication termination. In this study, through structural analysis combined with cell-based and biochemical assays, we identified that the PB1 Leu675/Asn676 and PB2 Arg38 residues of FluPol are critical for transcription termination and polyadenylation.

An intermediate state allows influenza polymerase to switch smoothly between transcription and replication cycles.

Influenza polymerase (FluPol) transcribes viral mRNA at the beginning of the viral life cycle and initiates genome replication after viral protein synthesis. However, it remains poorly understood how FluPol switches between its transcription and replication states, especially given that the structural bases of these two functions are fundamentally different. Here we propose a mechanism by which FluPol achieves functional switching between these two states through a previously unstudied conformation, termed an 'intermediate state'.

Antiviral Properties of Nanoparticles on Herpes Simplex Virus Type I and .

Herpes simplex virus type 1 (HSV-1), an enveloped DNA virus, plays a key role in varieties of diseases including recurrent cold sores, keratoconjunctivitis, genital herpes and encephalitis in humans. Great efforts have been made in developing more effective and less side-effects anti-herpes simplex virus agents, including traditional Chinese herbal medicines. In the present study, we evaluated the antiviral efficacy of nanoparticles against HSV-1 and .

Antiviral activity of arbidol hydrochloride against herpes simplex virus I in vitro and in vivo.

Herpes simplex virus type 1 (HSV-1) causes significant human diseases ranging from skin lesions to encephalitis, especially in neonates and immunocompromised hosts. The discovery of novel anti-HSV-1 drugs with low toxicity is required for public health. Arbidol hydrochloride (ARB) is an indole derivative molecule with broad-spectrum antiviral activity.

Chaetochromones A - C, Three New Polyketides from Mangrove Plant Derived Endophytic Fungus Phomopsis sp. SCSIO 41006.

Three new polyketides, chaetochromones A - C (1 - 3), together with a chromone (4), were isolated from the ethyl acetate extract of mangrove-derived fungus Phomopsis sp. SCSIO 41006. Their structures were elucidated by means of spectroscopic techniques (UV, IR, MS, 1D- and 2D-NMR).

Pentafluorosulfanyl-Substituted Benzopyran Analogues As New Cyclooxygenase-2 Inhibitors with Excellent Pharmacokinetics and Efficacy in Blocking Inflammation.

In this report, we disclose the design and synthesis of a series of pentafluorosulfanyl (SF) benzopyran derivatives as novel COX-2 inhibitors with improved pharmacokinetic and pharmacodynamic properties. The pentafluorosulfanyl compounds showed both potency and selectivity for COX-2 and demonstrated efficacy in several murine models of inflammation and pain. More interestingly, one of the compounds, R,S-3a, revealed exceptional efficacy in the adjuvant induced arthritis (AIA) model, achieving an ED as low as 0.

Discovery of new chemical entities as potential leads against Mycobacterium tuberculosis.

A series of biheterocyclic (1H-indole, benzofuran, pyrazolo[1,5-a]pyrimidine, pyrazolo[1,5-a]pyrimidin-5(4H)-one, imidazo[2,1-b]thiazole and pyrazolo[5,1-b]thiazole) derivatives were synthesized and evaluated for their anti-tubercular activities. The imidazo[2,1-b]thiazoles 9a-c and pyrazolo[5,1-b]thiazoles 10a-c exhibited promising anti-tubercular activity in varying degrees. Especially, the 2,6-dimethylpyrazolo[5,1-b]thiazole 10a exhibited strong suppressing function against H37Ra strain with MIC value of 0.

Design, synthesis, and in vitro biological evaluation of novel 6-methyl-7-substituted-7-deaza purine nucleoside analogs as anti-influenza A agents.

Among many subtypes of influenza A viruses, influenza A(H1N1) and A(H3N2) subtypes are currently circulating among humans (WHO report 2014-15). Therapeutically, the emergence of viral resistance to currently available drugs (adamantanes and neuraminidase inhibitors) has heightened alarms for developing novel drugs that could address diverse targets in the viral replication cycle in order to improve treatment outcomes. To this regard, the design and synthesis of nucleoside analog inhibitors as potential anti-influenza A agents is a very active field of research nowadays.