The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption 1,2 . There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.

Highlights d Phosphoproteomics analysis of SARS-CoV-2-infected cells uncovers signaling rewiring d Infection promotes host p38 MAPK cascade activity and shutdown of mitotic kinases d Infection stimulates CK2-containing filopodial protrusions with budding virus d Kinase activity analysis identifies potent antiviral drugs and compounds

No abstract

We evaluate all the primitive divergences contributing to the 7-loop β-function of ɸ4 theory, i.e. all 59 diagrams that are free of subdivergences and hence give scheme-independent contributions. Guided by the association of diagrams with knots, we obtain analytical results for 56 diagrams. The remaining three diagrams, associated with the knots 10124, 10139, and 10152, are evaluated numerically, to 10 sf. Only one satellite knot with 11 crossings is encountered and the transcendental number associated with it is found. Thus we achieve an analytical result for the 6-loop contributions, and a numerical result at 7 loops that is accurate to one part in 1011. The series of ‘zig-zag’ counterterms, [Formula: see text], previously known for n=3, 4, 5, 6 loops, is evaluated to 10 loops, corresponding to 17 crossings, revealing that the n-loop zig-zag term is [Formula: see text], where [Formula: see text] are the Catalan numbers, familiar in knot theory. The investigations reported here entailed intensive use of REDUCE, to generate O(104) lines of code for multiple precision FORTRAN computations, enabled by Bailey’s MPFUN routines, running for O(103) CPUhours on DecAlpha machines.

We provide a data mine of proven results for multiple zeta values (MZVs) of the form ζ(s 1

Abstract. Historically, the polylogarithm has attracted specialists and nonspecialists alike with its lovely evaluations. Much the same can be said for Euler sums (or multiple harmonic sums), which, within the past decade, have arisen in combinatorics, knot theory and high-energy physics. More recently, we have been forced to consider multidimensional extensions encompassing the classical polylogarithm, Euler sums, and the Riemann zeta function. Here, we provide a general framework within which previously isolated results can now be properly understood. Applying the theory developed herein, we prove several previously conjectured evaluations, including an intriguing conjecture of Don Zagier.

Heavy-light QCD currents are matched with heavy-quark effective theory (HQET) currents at two loops and leading order in l l m . A single formula applies to all current matchings. As a byproduct, a master formula for the two-loop anomalous dimension of the QCD current u[@l . . . yPnlq is obtained, yielding a new result for the tensor current. The dependence of matching coefficients on y~ prescriptions is elucidated. Ratios of QCD matrix elements are obtained, independently of the three-loop anomalous dimension of HQET currents. The two-loop coefficient in f~. / f~ =6.37 + A, with N1 = 4 light flavors, and a correction A, = 0.18 f 0.01 that takes account of the nonzero ratio m,/mb = 0.28 i 0 . 0 3 . Convergence of the perturbative series is poor: fastest apparent convergence would entail a,(p) at p = 370 MeV. "Naive non-Abelianisation" of large-Nl results, via Nl + Nl -T, gives reasonable approximations to exact two-loop results. All-order results for anomalous dimensions and matching coefficients are obtained at large ,L?o = 11 -$Nl. Consistent cancellation between infrared-and ultraviolet-renormalon ambiguities is demonstrated. PACS number(s): 12.39.Hg, ll.lO.Gh, 12.38.Bx, 12.38.Cy I. I N T R O D U C T I O NQCD problems with a single heavy quark staying approximately a t rest are conveniently described by a n effective field theory-heavy-quark effective field theory (HQET) [1,2] (see [3] for a review and references). QCD operators are expanded, in powers of l l m , in terms of H Q E T operators, m being the on-shell heavy-quark mass. In this paper we study, a t the two-loop level, the relation between currents in the full theory and the effective theory. Specifically, we consider heavy-light bilinear currents Jo = gorQo, where l7 is a Dirac matrix and the subscript 0 denotes a n unrenormalized quantity. The modified minimal subtraction scheme (m) renormalized QCD current J ( p ) = Z y l ( p ) Jo is expanded in H Q E T operators as where J ( p ) = 2y1(p)Jo is the corresponding renormalized H Q E T current, Jo = cfoI'Qo is the unrenormalized H Q E T current, Qo i s p two-component static-quark field, satisfying yoQo = Qo, a n d O i ( p ) are dimension-4 HQET operators, with appropriate quantum numbers. The meaning of the operator expansion (1.1) is that ma-'Electronic address: D.Broadhurst@open.ac.uk +~lectronic address: A.Grosin@open.ac.uk; on leave of absence from the Budker Institute of Nuclear Physics, Novosibirsk 630090, Russia. trix elements of J ( p ) , in situations amendable to H Q E T treatment, after expansion to a given order in l l m , coincide with the corresponding matrix elements of the righthand side of this equation. / 3 = -d In a,/d In p . The matching coefficient Cr(,u), for any l7 of the form (1.2), was obtained a t the one-loop level by Eichten and Hill [I]. T h e l l m suppressed matching coefficients B i ( p ) in (1.1) were obtained for vector and axial vector currents, a t one loop, in [4,5]. Here we shall find the two-loop correction t o the leading matching coefficient cr (PI.4082

It is found that the number, M n , of irreducible multiple zeta values (MZVs) of weight n, is generated by 1 − x 2 − x 3 = n (1 − x n ) Mn . For 9 ≥ n ≥ 3, M n enumerates positive knots with n crossings. Positive knots to which field theory assigns knot-numbers that are not MZVs first appear at 10 crossings. We identify all the positive knots, up to 15 crossings, that are in correspondence with irreducible MZVs, by virtue of the connection between knots and numbers realized by Feynman diagrams with up to 9 loops. * ) Work supported in part by grant CHRX-CT94-0579, from HUCAM.