Matrine combined with Osthole inhibited the PERK apoptosis of splenic lymphocytes in PCV2-infected mice model.

BACKGROUND: Porcine circovirus type 2 (PCV2) is one of the major pathogens commonly found in pigs, which causes immunosuppression and apoptosis. Vaccination and a single drug cannot totally prevent and treat PCV2 infection. Our previous in vitro study reported that the synergistic anti-PCV2 effect of Matrine and Osthole was better than that of Matrine or Osthole alone, This study was aimed to evaluate the synergistic anti-PCV2 effect as well as the underline molecular mechanism of Matrine and Osthole in Kunming (KM) mice model infected with PCV2. KM mice were randomly divided into 8 groups namely control group, PCV2 infected, Matrine combined with Osthole high dose treatment (40 mg/kg + 12 mg/kg), medium dose treatment (20 mg/kg + 6 mg/kg), low dose treatment (10 mg/kg + 3 mg/kg), Matrine treatment (40 mg/kg), Osthole treatment (12 mg/kg) and Ribavirin positive control (40 mg/kg) groups. PCV2 was intraperitoneally (i.p.) injected in all mice except the control group. 5 days of post-infection (dpi), mice in different treatment groups were injected i.p. with various doses of Matrine, Osthole and Ribavirin once daily for the next 5 consecutive days. RESULTS: The synergistic inhibitory effect of Matrine and Osthole on PCV2 replication in mouse liver was significantly heigher than that of Matrine and Osthole alone. The expression of GRP78, p-PERK, p-eIF2α, ATF4, CHOP, cleaved caspase-3 and Bax proteins were significantly reduced, while that of Bcl-2 was significantly increased in Matrine combined with Osthole groups, which alleviated the pathological changes caused by PCV2, such as interstitial pneumonia, loss of spleen lymphocytes, infiltration of macrophages and eosinophils. CONCLUSIONS: The synergistic anti-apoptotic effect of Matrine and Osthole was better than their alone effect, Both Matrine and Osthole had directly inhibited the expression of PCV2 Cap and the apoptosis of spleen cells induced by PCV2 Cap through the PERK pathway activated by endoplasmic reticulum (ER) GRP78. These results provided a new insight to control PCV2 infection and provide good component prescription candidate for the development of novel anti-PCV2 drugs.

A perspective on SARS-CoV-2 virus-like particles vaccines.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first appeared in Wuhan, China, in December 2019. The 2019 coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2, has spread to almost all corners of the world at an alarming rate. Vaccination is important for the prevention and control of the COVID-19 pandemic. Efforts are underway worldwide to develop an effective vaccine against COVID-19 using both traditional and innovative vaccine strategies. Compared to other vaccine platforms, SARS-CoV-2 virus-like particles （VLPs ）vaccines, as a new vaccine platform, have unique advantages: they have artificial nanostructures similar to natural SARS-CoV-2, which can stimulate good cellular and humoral immune responses in the organism; they have no viral nucleic acids, have good safety and thermal stability, and can be mass-produced and stored; their surfaces can be processed and modified, such as the adjuvant addition, etc.; they can be considered as an ideal platform for COVID-19 vaccine development. This review aims to shed light on the current knowledge and progress of VLPs vaccines against COVID-19, especially those undergoing clinical trials.