Cryo-EM structure of endogenous Pfs230 and Pfs48/45 fertilization complex.

Malaria parasite fertilization occurs in the midgut of a female mosquito. Blocking fertilization within the mosquito can prevent malaria transmission. Pfs230 and Pfs48/45 are critical for male fertility and transmission of the malaria parasite.

Photocatalytic 1,2-Dicarboxylation of Unactivated Alkynes with CO.

The carboxylation of widely available raw materials with CO represents a highly desirable transformation in synthetic chemistry, enabling the streamlined synthesis of valuable carboxylic acids. While the photocatalytic carboxylation of activated unsaturated compounds with CO has emerged as a powerful strategy for accessing diverse carboxylated products, the direct carboxylation of unactivated alkynes with CO remains a formidable challenge due to the intrinsic inertness of both aliphatic alkynes and CO. Herein, we report the first visible-light photocatalytic 1,2-dicarboxylation of unactivated alkynes with CO, providing a versatile platform for synthesizing structurally diverse succinic acid derivatives.

Stabilized designs of the malaria adhesin protein PvRBP2b for use as a potential diagnostic for Plasmodium vivax.

Plasmodium vivax is emerging as the most prevalent species causing malaria outside Africa. Most P. vivax infections are relapses due to the reactivation of the dormant liver stage parasites (hypnozoites).

Human coronavirus OC43 nanobody neutralizes virus and protects mice from infection.

Unlabelled: Human coronavirus (hCoV) OC43 is endemic to global populations and usually causes asymptomatic or mild upper respiratory tract illness. Here, we demonstrate the neutralization efficacy of isolated nanobodies from alpacas immunized with the S1 and S1 domain of the hCoV-OC43 spike glycoprotein. A total of 40 nanobodies bound to recombinant OC43 protein with affinities ranging from 1 to 149 nM.

Corrigendum: Fc engineered ACE2-Fc is a potent multifunctional agent targeting SARS-CoV2.

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Nanobodies against Pfs230 block Plasmodium falciparum transmission.

Transmission blocking interventions can stop malaria parasite transmission from mosquito to human by inhibiting parasite infection in mosquitos. One of the most advanced candidates for a malaria transmission blocking vaccine is Pfs230. Pfs230 is the largest member of the 6-cysteine protein family with 14 consecutive 6-cysteine domains and is expressed on the surface of gametocytes and gametes.

Structure of the Pf12 and Pf41 heterodimeric complex of 6-cysteine proteins.

During the different stages of the life cycle, surface-associated proteins establish key interactions with the host and play critical roles in parasite survival. The 6-cysteine (6-cys) protein family is one of the most abundant surface antigens and expressed throughout the life cycle. This protein family is conserved across species and plays critical roles in parasite transmission, evasion of the host immune response and host cell invasion.

Comparison of total immunoglobulin G antibody responses to different protein fragments of Plasmodium vivax Reticulocyte binding protein 2b.

Background: Plasmodium vivax is emerging as the dominant and prevalent species causing malaria in near-elimination settings outside of Africa. Hypnozoites, the dormant liver stage parasite of P. vivax, are undetectable to any currently available diagnostic test, yet are a major reservoir for transmission.

Landscape of human antibody recognition of the SARS-CoV-2 receptor binding domain.

Potent neutralizing monoclonal antibodies are one of the few agents currently available to treat COVID-19. SARS-CoV-2 variants of concern (VOCs) that carry multiple mutations in the viral spike protein can exhibit neutralization resistance, potentially affecting the effectiveness of some antibody-based therapeutics. Here, the generation of a diverse panel of 91 human, neutralizing monoclonal antibodies provides an in-depth structural and phenotypic definition of receptor binding domain (RBD) antigenic sites on the viral spike.

Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice.

Neutralizing antibodies are important for immunity against SARS-CoV-2 and as therapeutics for the prevention and treatment of COVID-19. Here, we identified high-affinity nanobodies from alpacas immunized with coronavirus spike and receptor-binding domains (RBD) that disrupted RBD engagement with the human receptor angiotensin-converting enzyme 2 (ACE2) and potently neutralized SARS-CoV-2. Epitope mapping, X-ray crystallography, and cryo-electron microscopy revealed two distinct antigenic sites and showed two neutralizing nanobodies from different epitope classes bound simultaneously to the spike trimer.

Naturally acquired blocking human monoclonal antibodies to Plasmodium vivax reticulocyte binding protein 2b.

Plasmodium vivax preferentially invades reticulocytes and recognition of these cells is mediated by P. vivax Reticulocyte Binding Protein 2b (PvRBP2b) binding to human Transferrin receptor 1 (TfR1) and Transferrin (Tf). Longitudinal cohort studies in Papua New Guinea, Thailand and Brazil show that PvRBP2b antibodies are correlated with protection against P.

Nanobody generation and structural characterization of Plasmodium falciparum 6-cysteine protein Pf12p.

Surface-associated proteins play critical roles in the Plasmodium parasite life cycle and are major targets for vaccine development. The 6-cysteine (6-cys) protein family is expressed in a stage-specific manner throughout Plasmodium falciparum life cycle and characterized by the presence of 6-cys domains, which are β-sandwich domains with conserved sets of disulfide bonds. Although several 6-cys family members have been implicated to play a role in sexual stages, mosquito transmission, evasion of the host immune response and host cell invasion, the precise function of many family members is still unknown and structural information is only available for four 6-cys proteins.

Surface area-to-volume ratio, not cellular viscoelasticity, is the major determinant of red blood cell traversal through small channels.

The remarkable deformability of red blood cells (RBCs) depends on the viscoelasticity of the plasma membrane and cell contents and the surface area to volume (SA:V) ratio; however, it remains unclear which of these factors is the key determinant for passage through small capillaries. We used a microfluidic device to examine the traversal of normal, stiffened, swollen, parasitised and immature RBCs. We show that dramatic stiffening of RBCs had no measurable effect on their ability to traverse small channels.

Plasmodium vivax Reticulocyte Binding Proteins for invasion into reticulocytes.

Plasmodium vivax is responsible for most of the malaria infections outside Africa and is currently the predominant malaria parasite in countries under elimination programs. P. vivax preferentially enters young red cells called reticulocytes.

Cryo-EM structure of an essential Plasmodium vivax invasion complex.

Plasmodium vivax is the most widely distributed malaria parasite that infects humans. P. vivax invades reticulocytes exclusively, and successful entry depends on specific interactions between the P.

Transferrin receptor 1 is a reticulocyte-specific receptor for .

shows a strict host tropism for reticulocytes. We identified transferrin receptor 1 (TfR1) as the receptor for reticulocyte-binding protein 2b (PvRBP2b). We determined the structure of the N-terminal domain of PvRBP2b involved in red blood cell binding, elucidating the molecular basis for TfR1 recognition.