ScholarBank@NUShttps://scholarbank.nus.edu.sgThe DSpace digital repository system captures, stores, indexes, preserves, and distributes digital research material.Wed, 02 Dec 2020 07:09:43 GMT2020-12-02T07:09:43Z5071- Drug repurposing of pyrimidine analogs as potent antiviral compounds against human enterovirus A71 infection with potential clinical applicationshttps://scholarbank.nus.edu.sg/handle/10635/170664Title: Drug repurposing of pyrimidine analogs as potent antiviral compounds against human enterovirus A71 infection with potential clinical applications
Authors: Sun, J; Yogarajah, T; Lee, RCH; Kaur, P; Inoue, M; Tan, YW; Chu, JJH
Abstract: © 2020, The Author(s). Enterovirus A71 (EV-A71) is one of the aetiological agents for the hand, foot and mouth disease (HFMD) in young children and a potential cause of neurological complications in afflicted patients. Since its discovery in 1969, there remains no approved antiviral for EV-A71 and other HFMD-causing enteroviruses. We set out to address the lack of therapeutics against EV-A71 by screening an FDA-approved drug library and found an enrichment of hits including pyrimidine antimetabolite, gemcitabine which showed 90.2% of inhibition on EV-A71 infection. Gemcitabine and other nucleoside analogs, LY2334737 and sofosbuvir inhibition of EV-A71 infection were disclosed using molecular and proteomic quantification, and in vitro and in vivo efficacy evaluation. Gemcitabine displayed a significant reduction of infectious EV-A71 titres by 2.5 logs PFU/mL and was shown to target the early stage of EV-A71 viral RNA and viral protein synthesis process especially via inhibition of the RNA dependent RNA polymerase. In addition, the drug combination study of gemcitabine’s synergistic effects with interferon-β at 1:1 and 1:2 ratio enhanced inhibition against EV-A71 replication. Since gemcitabine is known to metabolize rapidly in vivo, other nucleoside analogs, LY2334737 and sofosbuvir conferred protection in mice against lethal EV-A71 challenge by potentially reducing the death rate, viral titers as well on virus-induced pathology in the limb muscle tissue of mice. Additionally, we found that gemcitabine is competent to inhibit other positive-sense RNA viruses of the Flaviviridae and Togaviridae family. Overall, these drugs provide new insights into targeting viral factors as a broad-spectrum antiviral strategy with potential therapeutic value for future development and are worthy of potential clinical application.
Tue, 01 Dec 2020 00:00:00 GMThttps://scholarbank.nus.edu.sg/handle/10635/1706642020-12-01T00:00:00Z
- Constructing differentially 4-uniform permutations over f22k via the switching methodhttps://scholarbank.nus.edu.sg/handle/10635/128904Title: Constructing differentially 4-uniform permutations over f22k via the switching method
Authors: Qu, L.; Tan, Y.; Tan, C.H.; Li, C.
Abstract: Many block ciphers use permutations defined on f22k with low differential uniformity, high nonlinearity, and high algebraic degree as their S-boxes to provide confusion. It is well known that, for a function on ,f 2n the lowest differential uniformity is 2 and the functions achieving this lower bound are called almost perfect nonlinear (APN) functions. However, due to the lack of knowledge on APN permutations on f22k, differentially 4-uniform permutations are usually chosen as S-boxes. For example, the currently endorsed Advanced Encryption Standard chooses one such function, the multiplicative inverse function, as its S-box. By a recent survey on differentially 4-uniform permutations over f22k, there are only five known infinite families of such functions, and most of them have small algebraic degrees. In this paper, we apply the powerful switching method to discover many CCZ-inequivalent infinite families of such functions f 22k on with optimal algebraic degree, where k is an arbitrary positive integer. This greatly expands the list of differentially 4-uniform permutations and hence provide more choices for the S-boxes. Furthermore, lower bounds for the nonlinearity of the functions obtained in this paper are presented and they imply that some infinite families have high nonlinearity. © 2013 IEEE.
Mon, 01 Jul 2013 00:00:00 GMThttps://scholarbank.nus.edu.sg/handle/10635/1289042013-07-01T00:00:00Z
- Binomial differentially 4 uniform permutations with high nonlinearityhttps://scholarbank.nus.edu.sg/handle/10635/116938Title: Binomial differentially 4 uniform permutations with high nonlinearity
Authors: Bracken, C.; Tan, C.H.; Tan, Y.
Abstract: Differentially 4 uniform permutations with high nonlinearity on fields of even degree are crucial to the design of S-boxes in many symmetric cryptographic algorithms. Until now, there are not many known such functions and all functions known are power functions. In this paper, we construct the first class of binomial differentially 4 uniform permutations with high nonlinearity on F 26m, where m is an odd integer. This result gives a positive answer to an open problem proposed in Bracken and Leander (2010) [7]. © 2011 Elsevier Inc. All rights reserved.
Tue, 01 May 2012 00:00:00 GMThttps://scholarbank.nus.edu.sg/handle/10635/1169382012-05-01T00:00:00Z
- On the fourier spectra of new APN functionshttps://scholarbank.nus.edu.sg/handle/10635/116494Title: On the fourier spectra of new APN functions
Authors: Tan, Y.; Qu, L.; Ling, S.; Tan, C.H.
Abstract: Almost perfect nonlinear (APN) functions on F2n are functions achieving the lowest possible differential uniformity. All APN functions discovered until now are either power or quadratic ones, except for one sporadic multinomial nonquadratic example on F2 6 due to Edel and Pott. It is well known that certain binary codes with good properties can be obtained from APN functions, and determining their (Hamming) weight distribution is equivalent to determining the Fourier spectra of the corresponding functions. The Fourier spectra of all known infinite families of quadratic APN functions discovered through 2010 have been determined, and it was found that they are the same as the ones of the Gold APN functions, i.e., a 5-valued set when n is even and a 3-valued set when n is odd, while a sporadic example on F2 6 found by Dillon has a 7-valued Fourier spectrum. In 2011, two new generic constructions of APN functions were presented in [Y. Zhou and A. Pott, Adv. Math., 234 (2013), pp. 43-60] and [C. Carlet, Des. Codes Cryptogr., 59 (2011), pp. 89-109]. In this paper, we determine the Fourier spectra of the APN functions obtained from them and show that their Fourier spectra are again the same as those of the Gold APN functions. Moreover, since the APN functions in [C. Bracken, C. H. Tan, and Y. Tan, On a Class of Quadratic Polynomials with No Zeros and Its Applications to APN Functions, preprint, arXiv:1110.3177v1, 2011], which are demonstrated to exist when n ≡0 mod 4 and 3 | n, are covered by the construction in [C. Carlet, Des. Codes Cryptogr., 59 (2011), pp. 89-109], a positive answer to the conjecture proposed in the former paper on determining their Fourier spectrum is given in this paper. © 2013 Society for Industrial and Applied Mathematics.
Tue, 01 Jan 2013 00:00:00 GMThttps://scholarbank.nus.edu.sg/handle/10635/1164942013-01-01T00:00:00Z
- Association schemes arising from bent functionshttps://scholarbank.nus.edu.sg/handle/10635/117233Title: Association schemes arising from bent functions
Authors: Pott, A.; Tan, Y.; Feng, T.; Ling, S.
Abstract: We give a construction of 3-class and 4-class association schemes from s-nonlinear and differentially 2 s -uniform functions, and a construction of p-class association schemes from weakly regular p-ary bent functions, where p is an odd prime. © 2011 Springer Science+Business Media, LLC.
Fri, 01 Apr 2011 00:00:00 GMThttps://scholarbank.nus.edu.sg/handle/10635/1172332011-04-01T00:00:00Z
- On a class of quadratic polynomials with no zeros and its application to APN functionshttps://scholarbank.nus.edu.sg/handle/10635/117100Title: On a class of quadratic polynomials with no zeros and its application to APN functions
Authors: Bracken, C.; Tan, C.H.; Tan, Y.
Abstract: In [6], Lilya Budaghyan and Claude Carlet introduced a family of APN functions on F22k of the form F(x)=x(x2i+x2k+cx2k+i) +x2i(c2kx2k+δx2k+i)+x2k+i+2k. They showed that this infinite family exists provided the existence of the quadratic polynomial G(y)=y2i +1+cy2i+c2ky+1, which has no zeros such that y2k+1=1, or in particular has no zeros in F22k. However, up to now, no construction of such polynomials is known. In this paper, we show that, when k is an odd integer, the APN function F is CCZ-equivalent to the one in [2, Theorem 1]; and when k is even with 3â̂, we explicitly construct the polynomial G, and hence demonstrate the existence of F. More generally, it is well known that G relates to the polynomial ;bsupesupbsup. © 2013 Elsevier Inc. All rights reserved.
Wed, 01 Jan 2014 00:00:00 GMThttps://scholarbank.nus.edu.sg/handle/10635/1171002014-01-01T00:00:00Z
- New families of differentially 4-uniform permutations over double-struck F 22khttps://scholarbank.nus.edu.sg/handle/10635/117262Title: New families of differentially 4-uniform permutations over double-struck F 22k
Authors: Tan, Y.; Qu, L.; Tan, C.H.; Li, C.
Abstract: Differentially 4-uniform permutations over double-struck F 22k, especially those with high nonlinearity and high algebraic degree, are cryptographically significant mappings as they are good choices for the substitution boxes (S-boxes) in many symmetric ciphers. For instance, the currently endorsed Advanced Encryption Standard (AES) uses the inverse function, which is a differentially 4-uniform permutation. However, up to now, there are only five known infinite families of such mappings which attain the known maximal nonlinearity. Most of these five families have small algebraic degrees and only one family can be defined over double-struck F 22k for any positive integer k. In this paper, we apply the powerful switching method on the five known families to construct differentially 4-uniform permutations. New infinite families of such permutations are discovered from the inverse function, and some sporadic examples are found from the others by using a computer. All newly found infinite families can be defined over fields double-struck F 22k for any k and their algebraic degrees are 2k - 1. Furthermore, we obtain a lower bound for the nonlinearity of one infinite family. © 2012 Springer-Verlag.
Sun, 01 Jan 2012 00:00:00 GMThttps://scholarbank.nus.edu.sg/handle/10635/1172622012-01-01T00:00:00Z