Cross-reactive antibodies against human coronaviruses and the animal coronavirome suggest diagnostics for future zoonotic spillovers

The spillover of animal coronaviruses (aCoVs) to humans has caused SARS, MERS, and COVID-19. While antibody responses displaying cross-reactivity between SARS-CoV-2 and seasonal/common cold human coronaviruses (hCoVs) have been reported, potential cross-reactivity with aCoVs and the diagnostic implications are incompletely understood. Here, we probed for antibody binding against all seven hCoVs and 49 aCoVs represented as 12,924 peptides within a phage-displayed antigen library. Antibody repertoires of 269 recovered COVID-19 patients showed distinct changes compared to 260 unexposed pre-pandemic controls, not limited to binding of SARS-CoV-2 antigens but including binding to antigens from hCoVs and aCoVs with shared motifs to SARS-CoV-2. We isolated broadly reactive monoclonal antibodies from recovered COVID-19 patients that bind a shared motif of SARS-CoV-2, hCoV-OC43, hCoV-HKU1, and several aCoVs, demonstrating that interspecies cross-reactivity can be mediated by a single immunoglobulin. Employing antibody binding data against the entire CoV antigen library allowed accurate discrimination of recovered COVID-19 patients from unexposed individuals by machine learning. Leaving out SARS-CoV-2 antigens and relying solely on antibody binding to other hCoVs and aCoVs achieved equally accurate detection of SARS-CoV-2 infection. The ability to detect SARS-CoV-2 infection without knowledge of its unique antigens solely from cross-reactive antibody responses against other hCoVs and aCoVs suggests a potential diagnostic strategy for the early stage of future pandemics. Creating regularly updated antigen libraries representing the animal coronavirome can provide the basis for a serological assay already poised to identify infected individuals following a future zoonotic transmission event.

The molecular pH-response mechanism of the plant light-stress sensor PsbS

Plants need to protect themselves from excess light, which causes photo-oxidative damage and lowers the efficiency of photosynthesis. Photosystem II subunit S (PsbS) is a pH sensor protein that plays a crucial role in plant photoprotection by detecting thylakoid lumen acidification in excess light conditions via two lumen-faced glutamates. However, how PsbS is activated under low-pH conditions is unknown. To reveal the molecular response of PsbS to low pH, here we perform an NMR, FTIR and 2DIR spectroscopic analysis of Physcomitrella patens PsbS and of the E176Q mutant in which an active glutamate has been replaced. The PsbS response mechanism at low pH involves the concerted action of repositioning of a short amphipathic helix containing E176 facing the lumen and folding of the luminal loop fragment adjacent to E71 to a 310-helix, providing clear evidence of a conformational pH switch. We propose that this concerted mechanism is a shared motif of proteins of the light-harvesting family that may control thylakoid inter-protein interactions driving photoregulatory responses.

Asbestos and Salamander in India

The present paper, an homage to B. Laufer’s “Asbestos and Salamander” (1915), adds South Asia to the story of a remarkable Eurasian cultural meme meant to explain the presence of fire-proof cloth after its manufacturing technology was forgotten, namely that asbestos was the fur of a mythical animal. I argue that none of our Sanskrit dictionaries contain the correct meaning of the term agniśauca, which does indeed mean asbestos. The widely shared motif explains why in Sanskrit literature too we have animals (a nondescript mṛga) by the same name. I examine textual passages from kāvya, purāṇas, as well as Buddhist sūtras and śāstras, to elucidate this topic. I also cite some evidence that in the period between the 9th and the 11th c. some areas of India still possessed knowledge of asbestos manufacturing. However, as for where and when the correlation was first made, I must leave the question open.

Passage of transmissible cancers in the Tasmanian devil is due to a dominant, shared peptide motif and a limited repertoire of MHC-I allotypes

Transmissible cancers are spread via the passage of malignant cells. The survival of the Tasmanian devil, the largest marsupial carnivore, is threatened by two independent transmissible cancers, devil facial tumour (DFT) 1 and devil facial tumour 2 (DFT2). To aid the development of a peptide vaccine and to interrogate how histocompatibility barriers can be overcome, we analysed the peptides bound to Major Histocompatibility Complex class I molecules from the Tasmanian devil and its transmissible tumours. Comparison of the peptidomes from DFT1+IFNγ, DFT2 and host fibroblast cells demonstrates a shared motif, despite differences in MHC-I allotypes between the cell lines. Importantly, DFT1+IFNγ and DFT2 share the presentation of peptides derived from neural proteins, reflecting a common cellular origin that should be exploited for vaccine design. These results suggest that some polymorphisms between tumours and host are ‘hidden’ by a common peptide motif, providing the potential for permissive passage of infectious cells.