ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current VOCs and has surprising tolerance to mutations adjacent to or within its interaction epitope. Cryo-electron microscopy structure showed that 2G1 bound to the tip of receptor binding domain (RBD) of spike protein with small contact interface but strong hydrophobic effect, which resulted in nanomolar to sub-nanomolar affinities to spike proteins. The epitope of 2G1 on RBD partially overlaps with ACE2 interface, which gives 2G1 ability to block interaction between RBD and ACE2. The narrow binding epitope but high affinity bestow outstanding therapeutic efficacy upon 2G1 that neutralized VOCs with sub-nanomolar IC50 in vitro. In SARS-CoV-2 and Beta- and Delta-variant-challenged transgenic mice and rhesus macaque models, 2G1 protected animals from clinical illness and eliminated viral burden, without serious impact to animal safety. Mutagenesis experiments suggest that 2G1 could be potentially capable of dealing with emerging SARS-CoV-2 variants in future. This report characterized the therapeutic antibodies specific to the tip of spike against SARS-CoV-2 variants and highlights the potential clinical applications as well as for developing vaccine and cocktail therapy.
ABSTRACT
Objective To study the sugical treatment of elderly patients with acute intestinal ob-struction caused by colorectal cancer. Methods The clinical data of 56 elderly patients of acute colonic ob-struction caused by colorectal cancer from Janury 2002 to Janury 2007 were analyzed retrospectively. There were 20 cases with right side coloniclesion,32 cases with left side coloniclesion and 4 cases with rectal lesion. All patients received emergency operation. One stage tumor resection and anastomosis was performed in 20 cases with right side coloniclesion and in 25 cases with left side coloniclesion,Hartmann operation in 4 cases,proximal colostomy in 3 cases were performed with left side coloniclesion. Dixon operation in 2 cases and proximal colostomy in 3 cases were performed with rectum cancer. Results Postoperative complications occurred in 18 cases,including wound infection,intraperitoneal sepsis and intestinal fistula. Fifty-five cases recovered,there was one perioperative death. Conclusions Positive operation should be taken when the diagnosis of acute obstructing colorectal cancer the elderly is made. The operative methods depended on the patient'conditions. The perioperative managment should be emphasized and selection of rational operation procedure is important for decreasing mortality and complications of acute obstructing colorectal cancer in the elderly.
