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Background: The chemotherapy modality is generally used for treating colorectal cancer. However, the clinical application of chemotherapeutic drugs may be limited due to their adverse effects on normal cells/tissues and the development of cancer resistance. Using the combined treatment of chemotherapy drugs and natural bioactive compounds (such as resveratrol) can alleviate adverse drug reactions and induce synergies between the drugs. Objective: In the current review, the potential therapeutic impacts of resveratrol during colorectal cancer chemotherapy were studied. Method: Based on the PRISMA guideline, we performed a systematic search in different electronic databases up to May, 2021. Following the search, 321 papers were found and then screened for eligibility. Twenty-seven papers were finally included in the present study Results: Compared to the control group, the growth inhibition of cancerous cells treated with chemotherapeutic drugs was considerably higher, and resveratrol co-administration synergistically increased chemotherapy-induced cytotoxicity. Moreover, a reduction in the tumor weight, volume and growth of mice was observed following chemotherapy administration compared to the untreated groups, and these reductions were predominant in animals treated with resveratrol plus chemotherapy. Other findings showed that chemotherapy alone and in combination with resveratrol modulated the cell cycle profile of cancerous cells. Furthermore, chemotherapy treatment induced a set of biochemical and histopathological alterations in cancer cells/tissues, and these changes were synergized following resveratrol co-treatment (in most of the cases), excluding inflammatory mediators. Conclusions: In most cases, resveratrol co-administration could sensitize cancerous cells to chemotherapy drugs through its oxidant, apoptosis, anti-inflammatory activities, etc. Nevertheless, suggesting the use of resveratrol during chemotherapy of colorectal cancer patients requires further clinical studies.

A supramolecular assembly was constructed by morpholine-modified permethyl β-cyclodextrin, sulfonated porphyrin, and folic acid-modified chitosan via multivalent interactions, exhibiting promoted photodynamic effect and dual-targeted precise imaging.

Previous studies indicated inconsistent results for the treatment effect of repetitive transcranial magnetic stimulation (rTMS) on attention and memory impairment following stroke.: Randomized controlled trials (RCTs) on TMS for the treatment of stroke were retrieved from Online databases. Data were analyzed by RevMan 5.3 software.: Ten RCTs performed in China were included, with a total of 591 younger post-stroke patients ranging in age from their 40s to their 60s. The meta-analysis indicated that TMS could significantly improve the recovery of cognitive impairment following a stroke, according to the Montreal Cognitive Assessment (MoCA) score (8 studies, MD = 2.69, 95% CI: 1.44 to 3.95, P0.0001), the Rivermead Behavioral Memory Test (RBMT) score (7 studies, MD =1.74, 95% CI:1.13 to 2.34, P0.00001), and the Modified Barthel Index (MBI) for Activities of Daily Living (3 studies, MD =8.83, 95% CI:5.34 to 12.32, P0.00001). Sub-group analysis of MoCA and RBMT suggested that a low-frequency (1 Hz) stimulation exhibited similar effect with a higher-frequency (10 Hz) treatment.: TMS might effectively improve the attention and memory impairment of stroke patients without increasing side effects. But this effect needs to be verified by more multi-center, high-quality, large-sample, rigorously designed RCTs.

This study aims to explore the treatment efficacy of different motor rehabilitation interventions for upper limb impairment recovery.Publications were searched in PubMed and Embase. 4 grouped motor rehabilitation treatments (training, technological intervention, pharmacological intervention, and neuromodulation) were compared. The change of the Fugl-Meyer Assessment Scale for Upper Extremity (FMA-UE) was applied to assess upper limb function after stroke.56 studies including 5292 patients were identified. A significant difference was found among the 4 groups (P = 0.02). Neuromodulation interventions had the best treatment efficacy among the 4 types of interventions (P 0.01). Among neuromodulation interventions, acupuncture, electric, or magnetic intervention all had therapeutic efficacy for stroke upper limb recovery, without significant subgroup difference (P = 0.34). Stroke patients with mild upper limb impairment might not benefit from motor rehabilitation (P = 0.14).Neuromodulation interventions might have the best therapeutic efficacy among motor rehabilitation treatments for upper limb impairment after stroke. It is a potential treatment direction for upper limb recovery among stroke patients. However, since a large proportion of the original studies are low to very low-quality evidence, large-scale RCTs should be conducted in the future to validate current findings and assess treatment effects based on patient characteristics.

Cancer resistance to anti-tumour agents has been one of the serious challenges in different types of cancer treatment. Usually, an increase in the cell death markers can predict a higher rate of survival among patients diagnosed with cancer. By increasing the regulation of survival genes, cancer cells can display a higher resistance to therapy through the suppression of anti-tumour immunity and inhibition of cell death signalling pathways. Administration of certain adjuvants may be useful in order to increase the therapeutic efficiency of anti-cancer therapy through the stimulation of different cell death pathways. Several studies have demonstrated that metformin, an antidiabetic drug with anti-cancer properties, amplifies cell death mechanisms, especially apoptosis in a broad-spectrum of cancer cells. Stimulation of the immune system by metformin has been shown to play a key role in the induction of cell death. It seems that the induction or suppression of different cell death mechanisms has a pivotal role in either sensitization or resistance of cancer cells to therapy. This review explains the cellular and molecular mechanisms of cell death following anticancer therapy. Then, we discuss the modulatory roles of metformin on different cancer cell death pathways including apoptosis, mitotic catastrophe, senescence, autophagy, ferroptosis and pyroptosis.

Herein, the first example using commercially available 2-bromo-3,3,3-trifluoropropene (BTP) as a radical acceptor has been reported. Taking advantage of this strategy, a wide range of secondary trifluoromethylated alkyl bromides were synthesized in good to excellent yields with broad functional group tolerance by using redox-active esters as a radical precursor. The practicality of this protocol was further demonstrated by diverse derivations and direct modification of biologically active molecules.

Background Colorectal cancer (CRC) is one of the most malignant cancer worldwide, and the limited efficacy of existing treatments is the leading cause of death in patients with CRC. Thus, novel drugs for CRC treatment are urgently needed. Methods We screened an FDA-approved small-molecule library upon HCT116 cells, and identified lomitapide as a novel CRC anticancer compound. Then we confirmed the activities of lomitapide on CRC cells by WST-1 assay, colony formation, and flow cytometry. RNA sequencing and GO analysis were used to investigate the mechanisms underlying the anticancer effects of lomitapide. LiP-SMap was introduced to search for the potential targets of lomitapide. The in vivo experiment was conducted to confirm the therapeutic efficiency and safety of lomitapide as an anticancer agent. Results Lomitapide exhibited remarkable antitumor properties in vitro and in vivo, while activated autophagy is characterized by GO analysis as a key biological process in lomitapide-induced CRC repression. Moreover, lomitapide stimulated mitochondrial dysfunction-mediated AMPK activation, resulting in increased AMPK phosphorylation and enhanced Beclin1/Atg14/Vps34 interactions, provoking autophagy induction. LiP-SMap analysis showed that PP2A was the direct target of lomitapide, and the bioactivity of lomitapide was attenuated in PP2A-deficient cells, suggesting that the anticancer effect of lomitapide occurs in a PP2A-dependent manner. Conclusions Our results indicate that lomitapide activates AMPK-regulated autophagy to inhibit the proliferation and tumorigenesis of CRC cells by directly targeting PP2A, and can be a novel therapeutic agent for the treatment of CRC patients.

Cancer is a leading cause of death worldwide. Surgery is the primary treatment approach for cancer, but the survival rate is very low due to the rapid progression of the disease and presence of local and distant metastasis at diagnosis. Adjuvant chemotherapy and radiotherapy are important components of the multidisciplinary approaches for cancer treatment. However, resistance to radiotherapy and chemotherapy may result in treatment failure or even cancer recurrence. Radioresistance in cancer is often caused by the repair response to radiation‐induced DNA damage, cell cycle dysregulation, cancer stem cells (CSCs) resilience, and epithelial‐mesenchymal transition (EMT). Understanding the molecular alterations that lead to radioresistance may provide new diagnostic markers and therapeutic targets to improve radiotherapy efficacy. Patients who develop resistance to chemotherapy drugs cannot benefit from the cytotoxicity induced by the prescribed drug and will likely have a poor outcome with these treatments. Chemotherapy often shows a low response rate due to various drug resistance mechanisms. This review focuses on the molecular mechanisms of radioresistance and chemoresistance in cancer and discusses recent developments in therapeutic strategies targeting chemoradiotherapy resistance to improve treatment outcomes., This review discussed the molecular mechanisms of cancer resistance to radiotherapy and chemotherapy including enhanced DNA damage repair, reduced intracellular accumulation of drugs, drug inactivation, changes in drug targets, apoptosis‐growth balance disruption. We also focused on the roles of oncogenes and tumor suppressor genes in therapeutic resistance. Some anticancer drugs targeting oncogenes associated with therapeutic resistance were summarized.

Treatment of neuropathic pain (NP) resulting from nerve injury is one of the most complicated and challenging in modern practice. Pharmacological treatments for NP are not fully effectively and novel approaches are requisite. Recently, transplantation of bone mesenchymal stem cells (BMSCs) has represented a promising approach for pain relief and neural repair, but how it produces beneficial effects on resiniferatoxin (RTX) induced nerve injury is still unclear. Here, we identified the BMSCs' analgesic effects and their potential mechanisms of microglial cells activation on RTX induced neuralgia. Immunostaining, biochemical studies demonstrated that microglia rather than astrocyte cells activation involved in RTX induced mechanical hyperalgesia, whereas the GFP-labeled BMSCs alleviated this mechanical hyperalgesia. Moreover, pain-related TRPA1, PKCδ, CaMKIIɑ (Calcium/calmodulin dependent protein kinase II), P38/MAPK (mitogen-activated protein kinase), p-P65 activation and expression in the spinal cord were significantly inhibited after BMSC administration. In addition, BMSCs treated RTX mice displayed a lower density of mushroom dendritic spines. Our research suggested that activation of PKCδ-CaMKIIɑ-P38/MAPK-p-P65 pathway and mushroom dendritic spines abnormal increase in the spinal cord is the main mechanism of RTX induced neuropathic pain, and transplant of BMSCs to the damaged nerve may offer promising approach for neuropathic pain.

Rationale: Little is known about the roles of proteoglycans in esophageal cancer. This study aims to investigate the roles and mechanisms of serglycin (SRGN) proteoglycan in promoting metastasis of esophageal squamous cell carcinoma (ESCC). Methods: Reverse phase protein array analysis was used to identify activated signaling pathways in SRGN-overexpressing cells. Chemokine array was used to identify differentially secreted factors from SRGN-overexpressing cells. Binding between SRGN and potential interacting partners was evaluated using proximity ligation assay and co-immunoprecipitation. The glycosaminoglycan (GAG) chains of SRGN were characterized using fluorophore-assisted carbohydrate electrophoresis. Tissue microarray and serum samples were used to determine the correlation of SRGN expression with clinicopathological parameters and patient survival. Results: In vitro and in vivo experiments showed that SRGN promoted invasion and metastasis in ESCC via activating ERK pathway, stabilizing c-Myc and upregulating the secretion of matrix metalloproteinases. SRGN-knockdown suppressed tumorigenic hallmarks. These SRGN-elicited functions were carried out in an autocrine manner by inducing the secretion of midkine (MDK), which was further identified as a novel binding partner of SRGN for the formation of a SRGN/MDK/CD44 complex. In addition, SRGN interacted with MDK and matrix metalloproteinase 2 in ESCC via its GAG chains, which were mainly decorated with chondroitin sulfate comprising of ∆di-4S and ∆di-6S CS. Clinically, high expression of serum SRGN in serum of patients with ESCC was an independent prognostic marker for poor survival. Conclusions: This study provides the first evidence that elevated serum SRGN has prognostic significance in patients with ESCC, and sheds light on the molecular mechanism by which elevated circulating SRGN in cancer patients might promote cancer progression.

Esophageal cancer (EC) is one of the most lethal cancers in the world, and its morbidity and mortality rates rank among the top ten in China. Currently, surgical resection, radiotherapy and chemotherapy are the primary clinical treatments for esophageal cancer. However, outcomes are still unsatisfactory due to the limited efficacy and severe adverse effects of conventional treatments. As a new type of approach, targeted therapies have been confirmed to play an important role in the treatment of esophageal cancer; these include cetuximab and bevacizumab, which target epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), respectively. In addition, other drugs targeting surface antigens and signaling pathways or acting on immune checkpoints have been continuously developed. For example, trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER-2), has been approved by the Food and Drug Administration (FDA) as a first-line treatment of HER-2-positive cancer. Moreover, the PD-L1 inhibitor pembrolizumab has been approved as a highly efficient drug for patients with PD-L1-positive or advanced esophageal squamous cell carcinoma (ESCC). These novel drugs can be used alone or in combination with other treatment strategies to further improve the treatment efficacy and prognosis of cancer patients. Nevertheless, adverse events, optimal dosages and effective combinations still need further investigation. In this review, we expound an outline of the latest advances in targeted therapies of esophageal cancer and the mechanisms of relevant drugs, discuss their efficacy and safety, and provide a clinical rationale for precision medicine in esophageal cancer.

With its low-cost, label-free and non-destructive features, Raman spectroscopy is becoming an attractive technique with high potential to discriminate the causative agent of bacterial infections and bacterial infections per se. However, it is challenging to achieve consistency and accuracy of Raman spectra from numerous bacterial species and phenotypes, which significantly hinders the practical application of the technique. In this study, we analyzed surfaced enhanced Raman spectra (SERS) through machine learning algorithms in order to discriminate bacterial pathogens quickly and accurately. Two unsupervised machine learning methods, K-means Clustering (K-Means) and Agglomerative Nesting (AGNES) were performed for clustering analysis. In addition, eight supervised machine learning methods were compared in terms of bacterial predictions via Raman spectra, which showed that convolutional neural network (CNN) achieved the best prediction accuracy (99.86%) with the highest area (0.9996) under receiver operating characteristic curve (ROC). In sum, machine learning methods can be potentially applied to classify and predict bacterial pathogens via Raman spectra at general level.

A series of solid supramolecules based on acrylamide-phenylpyridium copolymers with various substituent groups (P-R: R=-CN, -CO

Colorectal cancer (CRC) is one of the most common malignant tumors in the world, with high prevalence and low 5-year survival. Most of the CRC patients show excessive activation of the Wnt/β-catenin pathway which is a vital target for CRC treatment. Based on multiple CRC cell lines with different nuclear expression of β-catenin, NU2058 is identified from a small molecule library consisting of 280 bioactive compounds and found to selectively inhibit the proliferation of CRC cells with nuclear β-catenin activation in vitro and in vivo. The translational significance of NU2058 alone or in combination with chemotherapeutic drugs oxaliplatin and irinotecan (SN38) in CRC is demonstrated in orthotopic tumor model and patient-derived xenograft models. By integrating limited proteolysis-small molecule mapping (LiP-SMap) and mass spectrometry (MS), Ran-binding protein 3 (RanBP3) is identified as the direct target of NU2058. The results show that RanBP3 is a tumor suppressor in CRC and is associated with patient survival. Mechanistically, NU2058 increases the interaction of RanBP3 and β-catenin to promote nuclear export of β-catenin, which further inhibits transcription of c-Myc and cyclin D1 to induce cell senescence. Collectively, NU2058 may serve as a promising therapeutic agent for CRC patients with selective disruption of pathologic Wnt/β-catenin signaling.

Background Cell invasion is a hallmark of metastatic cancer, leading to unfavorable clinical outcomes. In this study, we established two highly invasive lung cancer cell models (A549-i8 and H1299-i8) and identified mesoderm-specific transcript (MEST) as a novel invasive regulator of lung cancer. We aim to characterize its biological function and clinical significance in lung cancer metastasis. Methods Transwell invasion assay was performed to establish high-invasive lung cancer cell model. Immunohistochemistry (IHC) was used to detect MEST expression in tumor tissues. Mass spectrometry and bioinformatic analyses were used to identify MEST-regulated proteins and binding partners. Co-immunoprecipitation assay was performed to detect the interaction of MEST and VCP. The biological functions of MEST were investigated in vitro and in vivo. Immunofluorescence staining was conducted to explore the colocalization of MEST and VCP. Results MEST overexpression promoted metastasis of lung cancer cells in vivo and in vitro by activating NF-κB signaling. MEST increased the interaction between VCP and IκBα, which accelerated IκBα degradation and NF-κB activation. Such acceleration was abrogated by VCP silencing, indicating that MEST is an upstream activator of the VCP/IκBα/NF-κB signaling pathway. Furthermore, high expressions of MEST and VCP were associated with poor survival of lung cancer patients. Conclusion Collectively, these results demonstrate that MEST plays an important role in driving invasion and metastasis of lung cancer by interacting with VCP to coordinate the IκBα/NF-κB pathway. Targeting the MEST/VCP/IκBα/NF-κB signaling pathway may be a promising strategy to treat lung cancer.

Colorectal cancer (CRC) is one of the most lethal and prevalent solid malignancies worldwide. There is a great need of accelerating the development and diagnosis of CRC. Long noncoding RNAs (lncRNA) as transcribed RNA molecules play an important role in every level of gene expression. Metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1) is a highly conserved nucleus-restricted lncRNA that regulates genes at the transcriptional and post-transcriptional levels. High expression of MALAT1 is closely related to numerous human cancers. It is generally believed that MALAT1 expression is associated with CRC cell proliferation, tumorigenicity, and metastasis. MALAT1 by targeting multiple signaling pathways and microRNAs (miRNAs) plays a pivotal role in CRC pathogenesis. Therefore, MALAT1 can be a potent gene for cancer prediction and diagnosis. In this review, we will demonstrate signaling pathways associated with MALAT1 in CRC.

Cancer is one of the most difficult diseases in human society. Therefore, it is urgent for us to understand its pathogenesis and improve the cure rate. Exosomes are nanoscale membrane vesicles formed by a variety of cells through endocytosis. As a new means of intercellular information exchange, exosomes have attracted much attention. Noncoding RNAs exist in various cell compartments and participate in a variety of cellular reactions; in particular, they can be detected in exosomes bound to lipoproteins and free circulating molecules. Increasing evidence has suggested the potential roles of exosomal noncoding RNAs in the progression of tumors. Herein, we present a comprehensive update on the biological functions of exosomal noncoding RNAs in the development of cancer. Specifically, we mainly focus on the effects of exosomal noncoding RNAs, including microRNAs, circular RNAs, long noncoding RNAs, small nuclear RNAs, and small nucleolar RNAs, on tumor growth, metastasis, angiogenesis, and chemoresistance. Moreover, we outline the current clinical implications concerning exosomal noncoding RNAs in cancer treatment.

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway plays a crucial role in various cellular processes and is aberrantly activated in cancers, contributing to the occurrence and progression of tumors. Examining the upstream and downstream nodes of this pathway could allow full elucidation of its function. Based on accumulating evidence, strategies targeting major components of the pathway might provide new insights for cancer drug discovery. Researchers have explored the use of some inhibitors targeting this pathway to block survival pathways. However, because oncogenic PI3K pathway activation occurs through various mechanisms, the clinical efficacies of these inhibitors are limited. Moreover, pathway activation is accompanied by the development of therapeutic resistance. Therefore, strategies involving pathway inhibitors and other cancer treatments in combination might solve the therapeutic dilemma. In this review, we discuss the roles of the PI3K/Akt pathway in various cancer phenotypes, review the current statuses of different PI3K/Akt inhibitors, and introduce combination therapies consisting of signaling inhibitors and conventional cancer therapies. The information presented herein suggests that cascading inhibitors of the PI3K/Akt signaling pathway, either alone or in combination with other therapies, are the most effective treatment strategy for cancer.

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related death and has a poor prognosis worldwide, thus, more effective drugs are urgently needed. In this article, a small molecule drug library composed of 1,056 approved medicines from the FDA was used to screen for anticancer drugs. The tetracyclic compound maprotiline, a highly selective noradrenergic reuptake blocker, has strong antidepressant efficacy. However, the anticancer effect of maprotiline remains unclear. Here, we investigated the anticancer potential of maprotiline in the HCC cell lines Huh7 and HepG2. We found that maprotiline not only significantly restrained cell proliferation, colony formation and metastasis in vitro but also exerted antitumor effects in vivo. In addition to the antitumor effect alone, maprotiline could also enhance the sensitivity of HCC cells to sorafenib. The depth studies revealed that maprotiline substantially decreased the phosphorylation of sterol regulatory element-binding protein 2 (SREBP2) through the ERK signaling pathway, which resulted in decreased cholesterol biosynthesis and eventually impeded HCC cell growth. Furthermore, we identified cellular retinoic acid binding protein 1 (CRABP1) as a direct target of maprotiline. In conclusion, our study provided the first evidence showing that maprotiline could attenuate cholesterol biosynthesis to inhibit the proliferation and metastasis of HCC cells through the ERK-SREBP2 signaling pathway by directly binding to CRABP1, which supports the strategy of repurposing maprotiline in the treatment of HCC.

In this article, we propose a novel ultra-wideband, polarization-independent and wide-angle metamaterial absorber for the long-wave infrared region (8~14μm). The topology in this design is obtained by directly covering the surface of photoresist discs with a dielectric-metal-dielectric film, where the substrate supporting discs is a metal ground plane. The topology period is only 1.29 μm and the metamaterial absorber thickness is 1.305 μm. The broadband absorption of the entire long-wave infrared region mainly comes from resonance absorption at two wavelengths of 8.92 μm and 12.4 μm, and these two resonance absorptions are generated at different positions of the topology. The peak absorptions of the metamaterial absorber at 8.92 μm and 12.4 μm are 93.7% and 98.5%, respectively, and the average absorption in the infrared region of 8 to 14 microns is 91.6%. We calculate that the average absorption of the metamaterial absorber for TE mode still exceeds 85% up to an incident angle of 40°. However, for the TM mode, as the incident angle increases, the absorption increases. When the incident angle is 40°, the average absorption exceeds 95%. This metamaterial absorber with high performances in both bandwidth and absorptivity shows a promising prospect in applications such as thermal emitters, thermal coolers, and microbolometers.

Summary Four potent native human monoclonal antibodies (mAbs) targeting distinct epitopes on tetanus toxin (TeNT) are isolated with neutralization potency ranging from approximately 17 mg to 6 mg each that are equivalent to 250 IU of human anti-TeNT immunoglobulin. TT0170 binds fragment B, and TT0069 and TT0155 bind fragment AB. mAb TT0067 binds fragment C and blocks the binding of TeNT to gangliosides. The co-crystal structure of TT0067 with fragment C of TeNT at a 2.0-A resolution demonstrates that mAb TT0067 directly occupies the W pocket of one of the receptor binding sites on TeNT, resulting in blocking the binding of TeNT to ganglioside on the surface of host cells. This study reveals at the atomic level the mechanism of action by the TeNT neutralizing antibody. The key neutralization epitope on the fragment C of TeNT identified in our work provides the critical information for the development of fragment C of TeNT as a better and safer tetanus vaccine.

Aims & Objective: Coronavirus Disease 2019 (COVID-19) caused by the human coronavirus 2019 (HCoV-19, also known as SARS-CoV-2) infection is currently in a global outbreak. COVID-19 has posed a huge threat to public health and economic stability worldwide. CR3022, a human monoclonal neutralizing antibody isolated from a Severe Acute Respiratory Syndrome (SARS) recovery patient, was confirmed to be able to bind the S protein of HCoV-19 with a certain degree of neutralizing activity. Crystal structural information indicated that CR3022 could bind to the epitope on the receptor binding domain (RBD) of HCoV-19, whose epitope consists of 28 amino acids, and 24 of them are conserved in SARS-CoV of SARS. However, the crystal structure is only a static conformation at a certain moment in time, and it cannot provide dynamic details of the interaction between antigen and antibody. Methods: In this study, molecular dynamics (MD) simulation combined with MM/PBSA and CAS methods were performed to investigate the mechanism of binding of CR3022 against SARS-CoVRBD and HCoV-19-RBD in order to determine their holographic dynamic information. Results: It was found that the CR3022-SARS-CoV-RBD complex was more stable during 100ns MD run than that of the CR3022-HCoV-19-RBD system. There were common conservative amino acids on the β2 sheet of RBD, including Tyr369, Phe377, Lys378, Tyr380, Gly381, Lys386, Leu390 and others. These conservative amino acids play significant roles in the binding process of CR3022 antibody against SARS-CoV-RBD and HCoV-19-RBD. It was also found that the binding mode of CR3022 to its native target SARS-CoV-RBD is more comprehensive and uniform. Moreover, the β2 sheet residue Thr385 and non-β2 sheet residues Arg408 and Asp428 of the CR3022-SARS-CoV-RBD system were found to be crucial for their binding affinities, thus forming a special conformational epitope. However, these key amino acids are not present in the CR3022-HCoV-19-RBD system. The binding mode of CR3022 and HCoV-19-RBD is similar to that of SARS-CoV-RBD, but the deficiency of crucial hydrogen-bonds and salt-bridges. Therefore, the binding of CR3022 and HCoV-19-RBD only draws on the partial mode of the binding of CR3022 and SARS-CoV-RBD, so there is a loss of affinity. Conclusion: Thus, in order to better fight the epidemic of COVID-19 with the CR3022 antibody, this antibody needs to further improve the neutralization efficiency of HCoV-19 through mutation of it’s CDR region.