Spike mutation T403R allows bat coronavirus RaTG13 to use human ACE2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the COVID-19 pandemic, most likely emerged from bats. A prerequisite for this devastating zoonosis was the ability of the SARS-CoV-2 Spike (S) glycoprotein to use human angiotensin-converting enzyme 2 (ACE2) for viral entry. Although the S protein of the closest related bat virus, RaTG13, shows high similarity to the SARS-CoV-2 S protein it does not efficiently interact with the human ACE2 receptor. Here, we show that a single T403R mutation allows the RaTG13 S to utilize the human ACE2 receptor for infection of human cells and intestinal organoids. Conversely, mutation of R403T in the SARS-CoV-2 S significantly reduced ACE2-mediated virus infection. The S protein of SARS-CoV-1 that also uses human ACE2 also contains a positive residue (K) at this position, while the S proteins of CoVs utilizing other receptors vary at this location. Our results indicate that the presence of a positively charged amino acid at position 403 in the S protein is critical for efficient utilization of human ACE2. This finding could help to predict the zoonotic potential of animal coronaviruses.

Differential modules on p-adic polyannuli

We consider variational properties of some numerical invariants, measuring convergence of local horizontal sections, associated to differential modules on polyannuli over a nonarchimedean field of characteristic 0. This extends prior work in the one-dimensional case of Christol, Dwork, Robba, Young, et al. Our results do not require positive residue characteristic; thus besides their relevance to the study of Swan conductors for isocrystals, they are germane to the formal classification of flat meromorphic connections on complex manifolds.

Some Properties of the Inversion Counting Function

Let 𝑕, 𝑘 be integers such that 0 < 𝑕 < 𝑘 and (𝑕, 𝑘) = 1. If 1 ≤ 𝑖 ≤ 𝑘 – 1, let 𝑟𝑖 be the least positive residue (mod 𝑘) of 𝑕𝑖. Let the permutation For 1 ≤ 𝑖 < 𝑗 ≤ 𝑘 – 1, if 𝑟𝑖 > 𝑟𝑗, this is called an inversion of σ 𝑕, 𝑘. Let 𝐼(𝑕, 𝑘) denote the total number of inversions of σ 𝑕, 𝑘. In this note, we prove several identities concerning 𝐼(𝑕, 𝑘).

Least Positive Residues and the Quadratic Character of Two

Let be the least positive residue modulo 2tk of (2j- l)h. Define ut to be the number of with l≤j≤2t-2k such that . At the Special Session in Combinatorial Number Theory at the 1977 Summer AMS Meeting Szekeres [2] asked for a simple proof that if (h, 2k)=1, thenHere a simple proof will be given for the following equivalent result.

Pairs of Consecutive Residues of Polynomials

Let p be a large prime and let ƒ(x) be a polynomial of fixed degree d ⩾ 4 with integral coefficients, say,1.1Recently Mordell (8) has considered the problem of estimating the least positive residue of ƒ(x) (mod p), that is, the unique integer l (0 ⩽ l ⩽ p — 1) such that the congruence1.2is soluble for r = l but not for r = 0, 1, … , l — 1.

The First Factor of the Class Number of a Cyclic Field

Let p be a fixed prime > 3. The first factor of the field R(ζ), where R is the rational field and , is determined by means of1.1,wherer is a primitive root (mod p), and ri is the least positive residue of ri (mod p).